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1.
bioRxiv ; 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38559004

ABSTRACT

Formin HOmology Domain 2-containing (FHOD) proteins are a subfamily of actin-organizing formins important for striated muscle development in many animals. We showed previously that absence of the sole FHOD protein, FHOD-1, from C. elegans results in thin body-wall muscles with misshapen dense bodies that serve as sarcomere Z-lines. We demonstrate here that actin polymerization by FHOD-1 is required for its function in muscle development, and that FHOD-1 cooperates with profilin PFN-3 for dense body morphogenesis, and profilins PFN-2 and PFN-3 to promote body-wall muscle growth. We further demonstrate dense bodies in fhod-1 and pfn-3 mutants are less stable than in wild type animals, having a higher proportion of dynamic protein, and becoming distorted by prolonged muscle contraction. We also observe accumulation of actin depolymerization factor/cofilin homolog UNC-60B in body-wall muscle of these mutants. Such accumulations may indicate targeted disassembly of thin filaments dislodged from unstable dense bodies, and may account for the abnormally slow growth and reduced strength of body-wall muscle in fhod-1 mutants. Overall, these results show the importance of FHOD protein-mediated actin assembly to forming stable sarcomere Z-lines, and identify profilin as a new contributor to FHOD activity in striated muscle development.

2.
Exp Cell Res ; 398(1): 112388, 2021 01 01.
Article in English | MEDLINE | ID: mdl-33221314

ABSTRACT

Previous work with cultured cells has shown transcription of muscle genes by serum response factor (SRF) can be stimulated by actin polymerization driven by proteins of the formin family. However, it is not clear if endogenous formins similarly promote SRF-dependent transcription during muscle development in vivo. We tested whether formin activity promotes SRF-dependent transcription in striated muscle in the simple animal model, Caenorhabditis elegans. Our lab has shown FHOD-1 is the only formin that directly promotes sarcomere formation in the worm's striated muscle. We show here FHOD-1 and SRF homolog UNC-120 both support muscle growth and also muscle myosin II heavy chain A expression. However, while a hypomorphic unc-120 allele blunts expression of a set of striated muscle genes, these genes are largely upregulated or unchanged by absence of FHOD-1. Instead, pharmacological inhibition of the proteasome restores myosin protein levels in worms lacking FHOD-1, suggesting elevated proteolysis accounts for their myosin deficit. Interestingly, proteasome inhibition does not restore normal muscle growth to fhod-1(Δ) mutants, suggesting formin contributes to muscle growth by some alternative mechanism. Overall, we find SRF does not depend on formin to promote muscle gene transcription in a simple in vivo system.


Subject(s)
Caenorhabditis elegans Proteins/metabolism , Formins/metabolism , Muscle, Striated/metabolism , Serum Response Factor/metabolism , Animals , Caenorhabditis elegans/embryology , Caenorhabditis elegans/metabolism , Caenorhabditis elegans Proteins/genetics , Cell Proliferation , Formins/genetics , Serum Response Factor/genetics
3.
Cytoskeleton (Hoboken) ; 77(10): 422-441, 2020 10.
Article in English | MEDLINE | ID: mdl-33103378

ABSTRACT

The striated body wall muscles of Caenorhabditis elegans are a simple model for sarcomere assembly. Previously, we observed deletion mutants for two formin genes, fhod-1 and cyk-1, develop thin muscles with abnormal dense bodies (the sarcomere Z-line analogs). However, this work left in question whether these formins work in a muscle cell autonomous manner, particularly since cyk-1(∆) deletion has pleiotropic effects on development. Using a fast acting temperature-sensitive cyk-1(ts) mutant, we show here that neither postembryonic loss nor acute loss of CYK-1 during embryonic sarcomerogenesis cause lasting muscle defects. Furthermore, mosaic expression of CYK-1 in cyk-1(∆) mutants is unable to rescue muscle defects in a cell autonomous manner, suggesting muscle phenotypes caused by cyk-1(∆) are likely indirect. Conversely, mosaic expression of FHOD-1 in fhod-1(Δ) mutants promotes muscle cell growth and proper dense body organization in a muscle cell autonomous manner. As we observe no effect of loss of any other formin on muscle development, we conclude FHOD-1 is the only worm formin that directly promotes striated muscle development, and the effects on formin loss in C. elegans are surprisingly modest compared to other systems.


Subject(s)
Caenorhabditis elegans/pathogenicity , Fetal Proteins/metabolism , Formins/metabolism , Muscle, Striated/metabolism , Animals
5.
Cytoskeleton (Hoboken) ; 76(4): 322-336, 2019 04.
Article in English | MEDLINE | ID: mdl-31215743

ABSTRACT

Epithelial cell-cell junctions have dual roles of accommodating morphological changes in an epithelium, while maintaining cohesion during those changes. An abundance of junction proteins has been identified, but many details on how intercellular junctions respond to morphological changes remain unclear. In Caenorhabditis elegans, the spermatheca is an epithelial sac that repeatedly dilates and constricts to allow ovulation. It is thought that the junctions between spermatheca epithelial cells undergo reversible partial unzipping to allow rapid dilation. Previously, we found that EXC-6, a C. elegans protein homolog of the human disease-associated formin INF2, is expressed in the spermatheca and promotes oocyte entry. We show here that EXC-6 localizes toward the apical aspect of the spermatheca epithelial junctions, and that the EXC-6-labeled junction domains "unzip" and dramatically flatten with oocyte entry into the spermatheca. We demonstrate that the C-terminal tail of EXC-6 is necessary and sufficient for junction localization. Moreover, expression of the tail alone worsens ovulation defects, suggesting this region not only mediates EXC-6 localization, but also interacts with other components important for junction remodeling.


Subject(s)
Caenorhabditis elegans Proteins/metabolism , Caenorhabditis elegans/metabolism , Epithelial Cells/metabolism , Animals , Cell Polarity , Humans , Intercellular Junctions
6.
G3 (Bethesda) ; 8(7): 2277-2290, 2018 07 02.
Article in English | MEDLINE | ID: mdl-29720391

ABSTRACT

The cytoskeleton is the basic machinery that drives many morphogenetic events. Elongation of the C. elegans embryo from a spheroid into a long, thin larva initially results from actomyosin contractility, mainly in the lateral epidermal seam cells, while the corresponding dorsal and ventral epidermal cells play a more passive role. This is followed by a later elongation phase involving muscle contraction. Early elongation is mediated by parallel genetic pathways involving LET-502/Rho kinase and MEL-11/MYPT myosin phosphatase in one pathway and FEM-2/PP2c phosphatase and PAK-1/p21 activated kinase in another. While the LET-502/MEL-11 pathway appears to act primarily in the lateral epidermis, here we show that FEM-2 can mediate early elongation when expressed in the dorsal and ventral epidermis. We also investigated the early elongation function of FHOD-1, a member of the formin family of actin nucleators and bundlers. Previous work showed that FHOD-1 acts in the LET-502/MEL-11 branch of the early elongation pathway as well as in muscle for sarcomere organization. Consistent with this, we found that lateral epidermal cell-specific expression of FHOD-1 is sufficient for elongation, and FHOD-1 effects on elongation appear to be independent of its role in muscle. Also, we found that fhod-1 encodes long and short isoforms that differ in the presence of a predicted coiled-coil domain. Based on tissue-specific expression constructions and an isoform-specific CRISPR allele, the two FHOD-1 isoforms show partially specialized epidermal or muscle function. Although fhod-1 shows only impenetrant elongation phenotypes, we were unable to detect redundancy with other C. elegans formin genes.


Subject(s)
Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans/embryology , Caenorhabditis elegans/genetics , Gene Expression Regulation, Developmental , Microfilament Proteins/genetics , Morphogenesis/genetics , Phosphoprotein Phosphatases/genetics , Alternative Splicing , Animals , Animals, Genetically Modified , Embryo, Nonmammalian , Epidermis/embryology , Epidermis/metabolism , Formins , Organ Specificity/genetics , Phenotype
7.
PLoS One ; 12(10): e0186081, 2017.
Article in English | MEDLINE | ID: mdl-28982189

ABSTRACT

Formins are proteins that assist in regulating cytoskeletal organization through interactions with actin filaments and microtubules. Metazoans encode nine distinct formin subtypes based on sequence similarity, potentially allowing for great functional diversity for these proteins. Through the evolution of the eukaryotes, formins are believed to have repeatedly undergone rounds of gene duplications, followed by diversification and domain shuffling, but previous phylogenetic analyses have shed only a little light on the specific origins of different formin subtypes. To improve our understanding of this in the case of the metazoan formins, phylogenetic comparisons were made here of a broad range of metazoan and non-metazoan formin sequences. This analysis suggests a model in which eight of the nine metazoan formin subtypes arose from two ancestral proteins that were present in an ancient unikont ancestor. Additionally, evidence is shown suggesting the common ancestor of unikonts and bikonts was likely to have encoded at least two formins, a canonical Drf-type protein and a formin bearing a PTEN-like domain.


Subject(s)
Evolution, Molecular , Microfilament Proteins/genetics , Animals , Phylogeny , Sequence Alignment
8.
Cytoskeleton (Hoboken) ; 74(11): 405-419, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28921928

ABSTRACT

Formins are a family of regulators of actin and microtubule dynamics that are present in almost all eukaryotes. These proteins are involved in many cellular processes, including cytokinesis, stress fiber formation, and cell polarization. Here we review one subfamily of formins, the inverted formins. Inverted formins as a group break several formin stereotypes, having atypical biochemical properties and domain organization, and they have been linked to kidney disease and neuropathy in humans. In this review, we will explore recent research on members of the inverted formin sub-family in mammals, zebrafish, fruit flies, and worms.


Subject(s)
Actins/metabolism , Cytoskeletal Proteins/metabolism , Nuclear Proteins/metabolism , Animals , Cytoskeletal Proteins/genetics , Formins , Humans , Mice
9.
Handb Exp Pharmacol ; 235: 39-75, 2017.
Article in English | MEDLINE | ID: mdl-27832381

ABSTRACT

In this chapter, we present the current knowledge on de novo assembly, growth, and dynamics of striated myofibrils, the functional architectural elements developed in skeletal and cardiac muscle. The data were obtained in studies of myofibrils formed in cultures of mouse skeletal and quail myotubes, in the somites of living zebrafish embryos, and in mouse neonatal and quail embryonic cardiac cells. The comparative view obtained revealed that the assembly of striated myofibrils is a three-step process progressing from premyofibrils to nascent myofibrils to mature myofibrils. This process is specified by the addition of new structural proteins, the arrangement of myofibrillar components like actin and myosin filaments with their companions into so-called sarcomeres, and in their precise alignment. Accompanying the formation of mature myofibrils is a decrease in the dynamic behavior of the assembling proteins. Proteins are most dynamic in the premyofibrils during the early phase and least dynamic in mature myofibrils in the final stage of myofibrillogenesis. This is probably due to increased interactions between proteins during the maturation process. The dynamic properties of myofibrillar proteins provide a mechanism for the exchange of older proteins or a change in isoforms to take place without disassembling the structural integrity needed for myofibril function. An important aspect of myofibril assembly is the role of actin-nucleating proteins in the formation, maintenance, and sarcomeric arrangement of the myofibrillar actin filaments. This is a very active field of research. We also report on several actin mutations that result in human muscle diseases.


Subject(s)
Actins/chemistry , Muscle Development , Muscle, Striated/cytology , Myofibrils/chemistry , Animals , Humans , Mice , Myofibrils/physiology , Myosins/chemistry , Polymerization , Sarcomeres , Zebrafish
10.
Cytoskeleton (Hoboken) ; 73(12): 712-728, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27770600

ABSTRACT

Formins are regulators of actin filament dynamics. We demonstrate here that two formins, FHOD-1 and EXC-6, are important in the nematode Caenorhabditis elegans for ovulation, during which actomyosin contractions push a maturing oocyte from the gonad arm into a distensible bag-like organ, the spermatheca. EXC-6, a homolog of the disease-associated mammalian formin INF2, is highly expressed in the spermatheca, where it localizes to cell-cell junctions and to circumferential actin filament bundles. Loss of EXC-6 does not noticeably affect the organization the actin filament bundles, and causes only a very modest increase in the population of junction-associated actin filaments. Despite absence of a strong cytoskeletal phenotype, approximately half of ovulations in exc-6 mutants exhibit extreme defects, including failure of the oocyte to enter the spermatheca, or breakage of the oocyte as the distal spermatheca entrance constricts during ovulation. Loss of FHOD-1 alone has little effect, and we cannot detect FHOD-1 in the spermatheca. However, combined loss of these formins in double fhod-1;exc-6 mutants results in profound ovulation defects, with significant slowing of the entry of oocytes into the spermatheca, and failure of nearly 80% of ovulations. We suggest that EXC-6 plays a role directly in the spermatheca, perhaps by modulating the ability of the spermatheca wall to rapidly accommodate an incoming oocyte, while FHOD-1 may play an indirect role relating to its known importance in the growth and function of the egg-laying muscles. © 2016 The Authors. Cytoskeleton Published by Wiley Periodicals, Inc.


Subject(s)
Actin Cytoskeleton/metabolism , Caenorhabditis elegans Proteins/metabolism , Caenorhabditis elegans/metabolism , Microfilament Proteins/metabolism , Oocytes/metabolism , Ovulation/metabolism , Actin Cytoskeleton/immunology , Animals , Caenorhabditis elegans/genetics , Caenorhabditis elegans Proteins/genetics , Female , Formins , Male , Microfilament Proteins/genetics , Ovulation/genetics
11.
PLoS One ; 11(10): e0164067, 2016.
Article in English | MEDLINE | ID: mdl-27695129

ABSTRACT

Formins are a widespread family of eukaryotic cytoskeleton-organizing proteins. Many species encode multiple formin isoforms, and for animals, much of this reflects the presence of multiple conserved subtypes. Earlier phylogenetic analyses identified seven major formin subtypes in animals (DAAM, DIAPH, FHOD, FMN, FMNL, INF, and GRID2IP/delphilin), but left a handful of formins, particularly from nematodes, unassigned. In this new analysis drawing from genomic data from a wider range of taxa, nine formin subtypes are identified that encompass all the animal formins analyzed here. Included in this analysis are Multiple Wing Hairs proteins (MWH), which bear homology to formin N-terminal domains. Originally identified in Drosophila melanogaster and other arthropods, MWH-related proteins are also identified here in some nematodes (including Caenorhabditis elegans), and are shown to be related to a novel MWH-related formin (MWHF) subtype. One surprising result of this work is the discovery that a family of pleckstrin homology domain-containing formins (PHCFs) is represented in many vertebrates, but is strikingly absent from placental mammals. Consistent with a relatively recent loss of this formin, the human genome retains fragments of a defunct homologous formin gene.


Subject(s)
Microfilament Proteins/classification , Microfilament Proteins/genetics , Phylogeny , Amino Acid Sequence , Animals , Evolution, Molecular , Hair , Humans , Microfilament Proteins/chemistry , Protein Domains/genetics , Wings, Animal
12.
J Cytol Histol ; 6(2)2015 Mar.
Article in English | MEDLINE | ID: mdl-26161293

ABSTRACT

Members of the formin family of actin filament nucleation factors have been implicated in sarcomere formation, but precisely how these proteins affect sarcomere structure remains poorly understood. Of six formins in the simple nematode Caenorhabditis elegans, only FHOD-1 and CYK-1 contribute to sarcomere assembly in the worm's obliquely striated body-wall muscles. We analyze here the ultrastructure of body-wall muscle sarcomeres in worms with putative null fhod-1 and cyk-1 gene mutations. Contrary to a simple model that formins nucleate actin for thin filament assembly, formin mutant sarcomeres contain thin filaments. Rather, formin mutant sarcomeres are narrower and have deformed thin filament-anchoring Z-line structures. Thus, formins affect multiple aspects of sarcomere structure.

13.
Biol Open ; 4(7): 843-51, 2015 May 15.
Article in English | MEDLINE | ID: mdl-25979704

ABSTRACT

eIF4E plays a conserved role in initiating protein synthesis, but with multiple eIF4E isoforms present in many organisms, these proteins also adopt specialized functions. Previous RNAi studies showed that ife-3, encoding the sole canonical eIF4E isoform of Caenorhabditis elegans, is essential for viability. Using ife-3 gene mutations, we show here that it is maternal ife-3 function that is essential for embryogenesis, but ife-3 null progeny of heterozygous animals are viable. We find that zygotic ife-3 function promotes body growth and regulates germline development in hermaphrodite worms. Specifically, the normal transition from spermatogenesis to oogenesis in the hermaphrodite germline fails in ife-3 mutants. This failure to switch is reversed by inhibiting expression of the key masculinizing gene, fem-3, suggesting ife-3 resembles a growing number of genes that promote the sperm/oocyte switch by acting genetically as upstream inhibitors of fem-3.

14.
Worm ; 2(3): e25040, 2013 Jul 01.
Article in English | MEDLINE | ID: mdl-24778933

ABSTRACT

During the second half of embryogenesis, the ellipsoidal Caenorhabditis elegans embryo elongates into a long, thin worm. This elongation requires a highly organized cytoskeleton composed of actin microfilaments, microtubules and intermediate filaments throughout the epidermis of the embryo. This architecture allows the embryonic epidermal cells to undergo a smooth muscle-like actin/myosin-based contraction that is redundantly controlled by LET- 502/Rho kinase and MEL-11/myosin phosphatase in one pathway and FEM-2/PP2c phosphatase and PAK-1/p21-activated kinase in a parallel pathway(s). Although actin microfilaments surround the embryo, the force for contraction is generated mainly in the lateral (seam) epidermal cells whose actin microfilaments appear qualitatively different from those in their dorsal/ventral neighbors. We have identified FHOD-1, a formin family actin nucleator, which acts in the lateral epidermis. fhod-1 mutants show microfilament defects in the embryonic lateral epidermal cells and FHOD-1 protein is detected only in those cells. fhod-1 genetic interactions with let-502, mel-11, fem-2 and pak-1 indicate that fhod-1 preferentially regulates those microfilaments acting with let-502 and mel-11, and in parallel to fem-2 and pak-1. Thus, FHOD-1 may contribute to the qualitative differences in microfilaments found in the contractile lateral epidermal cells and their non-contractile dorsal and ventral neighbors. Different microfilament populations may be involved in the different contractile pathways.

15.
J Cell Biol ; 198(1): 87-102, 2012 Jul 09.
Article in English | MEDLINE | ID: mdl-22753896

ABSTRACT

Muscle contraction depends on interactions between actin and myosin filaments organized into sarcomeres, but the mechanism by which actin filaments incorporate into sarcomeres remains unclear. We have found that, during larval development in Caenorhabditis elegans, two members of the actin-assembling formin family, CYK-1 and FHOD-1, are present in striated body wall muscles near or on sarcomere Z lines, where barbed ends of actin filaments are anchored. Depletion of either formin during this period stunted growth of the striated contractile lattice, whereas their simultaneous reduction profoundly diminished lattice size and number of striations per muscle cell. CYK-1 persisted at Z lines in adulthood, and its near complete depletion from adults triggered phenotypes ranging from partial loss of Z line-associated filamentous actin to collapse of the contractile lattice. These results are, to our knowledge, the first genetic evidence implicating sarcomere-associated formins in the in vivo organization of the muscle cytoskeleton.


Subject(s)
Caenorhabditis elegans Proteins/metabolism , Caenorhabditis elegans/growth & development , Microfilament Proteins/metabolism , Muscle, Striated/growth & development , Muscle, Striated/metabolism , Sarcomeres/metabolism , Animals , Caenorhabditis elegans/metabolism , Caenorhabditis elegans Proteins/genetics , Formins , Microfilament Proteins/genetics
16.
Methods ; 56(1): 11-7, 2012 Jan.
Article in English | MEDLINE | ID: mdl-21945576

ABSTRACT

The nematode Caenorhabditis elegans has long been a useful model organism for muscle research. Its body wall muscle is obliquely striated muscle and exhibits structural similarities with vertebrate striated muscle. Actin is the core component of the muscle thin filaments, which are highly ordered in sarcomeric structures in striated muscle. Genetic studies have identified genes that regulate proper organization and function of actin filaments in C. elegans muscle, and sequence of the worm genome has revealed a number of conserved candidate genes that may regulate actin. To precisely understand the functions of actin-binding proteins, such genetic and genomic studies need to be complemented by biochemical characterization of these actin-binding proteins in vitro. This article describes methods for purification and biochemical characterization of actin from C. elegans. Although rabbit muscle actin is commonly used to characterize actin-binding proteins from many eukaryotic organisms, we detect several quantitative differences between C. elegans actin and rabbit muscle actin, highlighting that use of actin from an appropriate source is important in some cases. Additionally, we describe probes for cell biological analysis of actin in C. elegans.


Subject(s)
Actins/metabolism , Caenorhabditis elegans/metabolism , Animals , Blotting, Western , Combinatorial Chemistry Techniques , Electrophoresis, Polyacrylamide Gel , Humans , Rabbits
17.
Adv Exp Med Biol ; 644: 168-86, 2008.
Article in English | MEDLINE | ID: mdl-19209822

ABSTRACT

Tropomyosins were discovered as regulators of actomyosin contractility in muscle cells, making yeasts and other fungi seem unlikely to harbor such proteins. Fungal cells are encased in a rigid cell wall and do not engage in the same sorts of contractile shape changes of animal cells. However, discovery of actin and myosin in yeast raised the possibility for a role for tropomyosin in regulating their interaction. Through a biochemical search, fungal tropomyosins were identified with strong similarities to their animal counterparts in terms ofprotein structure and physical properties. Two particular fungi, the buddingyeast Saccharomyces cerevisiae and the fission yeast Schizosaccharomyces pombe, have provided powerful genetic systems for studying tropomyosins in nonmetazoans. In these yeasts, tropomyosins associate with subsets ofactin filamentous structures. Mutational studies oftropomyosin genes and biochemical assays of purified proteins point to roles for these proteins as factors that stabilize actin filaments, promote actin-based structures of particular architecture and help maintain distinct biochemical identities among different filament populations. Tropomyosin-enriched filaments are the cytoskeletal structures that promote the major cell shape changes of these organisms: polarized growth and cell division.


Subject(s)
Saccharomyces cerevisiae/metabolism , Schizosaccharomyces/metabolism , Tropomyosin/physiology , Actins/chemistry , Amino Acid Sequence , Biochemistry/methods , Cell Division , Fungal Proteins/metabolism , Gene Expression Regulation, Fungal , Models, Biological , Molecular Conformation , Molecular Sequence Data , Phylogeny , Sequence Homology, Amino Acid , Species Specificity , Tropomyosin/chemistry
18.
Development ; 134(1): 19-29, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17138663

ABSTRACT

Striated muscle development in vertebrates requires the redundant functions of multiple members of the MyoD family. Invertebrates such as Drosophila and Caenorhabditis elegans contain only one MyoD homolog in each organism. Earlier observations suggest that factors outside of the MyoD family might function redundantly with MyoD in striated muscle fate specification in these organisms. However, the identity of these factors has remained elusive. Here, we describe the identification and characterization of FOZI-1, a putative transcription factor that functions redundantly with CeMyoD (HLH-1) in striated body wall muscle (BWM) fate specification in the C. elegans postembryonic mesoderm. fozi-1 encodes a novel nuclear-localized protein with motifs characteristic of both transcription factors and actin-binding proteins. We show that FOZI-1 shares the same expression pattern as CeMyoD in the postembryonic mesodermal lineage, the M lineage, and that fozi-1-null mutants exhibit similar M lineage-null defects to those found in animals lacking CeMyoD in the M lineage (e.g. loss of a fraction of M lineage-derived BWMs). Interestingly, fozi-1-null mutants with a reduced level of CeMyoD lack most, if not all, M lineage-derived BWMs. Our results indicate that FOZI-1 and the Hox factor MAB-5 function redundantly with CeMyoD in the specification of the striated BWM fate in the C. elegans postembryonic mesoderm, implicating a remarkable level of complexity for the production of a simple striated musculature in C. elegans.


Subject(s)
Caenorhabditis elegans Proteins/metabolism , Caenorhabditis elegans/embryology , Mesoderm/physiology , Muscle Proteins/metabolism , Muscle, Skeletal/embryology , Nuclear Proteins/metabolism , Transcription Factors/metabolism , Alleles , Amino Acid Motifs , Amino Acid Sequence , Animals , Caenorhabditis elegans/genetics , Caenorhabditis elegans Proteins/chemistry , Caenorhabditis elegans Proteins/genetics , Cell Differentiation , Cell Lineage , Embryo, Nonmammalian , Gene Expression Regulation, Developmental , Intercellular Signaling Peptides and Proteins , Mesoderm/cytology , Models, Biological , Molecular Sequence Data , Organisms, Genetically Modified , Protein Structure, Tertiary , RNA Interference , Recombinant Proteins/isolation & purification , Recombinant Proteins/metabolism , Zinc Fingers
19.
Annu Rev Cell Dev Biol ; 20: 559-91, 2004.
Article in English | MEDLINE | ID: mdl-15473852

ABSTRACT

Cell polarity, as reflected by polarized growth and organelle segregation during cell division in yeast, appears to follow a simple hierarchy. On the basis of physical cues from previous cell cycles or stochastic processes, yeast cells select a site for bud emergence that also defines the axis of cell division. Once polarity is established, rho protein-based signal pathways set up a polarized cytoskeleton by activating localized formins to nucleate and assemble polarized actin cables. These serve as tracks for the transport of secretory vesicles, the segregation of the trans Golgi network, the vacuole, peroxisomes, endoplasmic reticulum, mRNAs for cell fate determination, and microtubules that orient the nucleus in preparation for mitosis, all by myosin-Vs encoded by the MYO2 and MYO4 genes. Most of the proteins participating in these processes in yeast are conserved throughout the kingdoms of life, so the emerging models are likely to be generally applicable. Indeed, several parallels to cellular organization in animals are evident.


Subject(s)
Saccharomyces cerevisiae/growth & development , Saccharomyces cerevisiae/ultrastructure , Actins/metabolism , Animals , Cell Division/physiology , Cell Polarity/physiology , Cytoskeleton/metabolism , Organelles/metabolism , Saccharomyces cerevisiae/metabolism
20.
Mol Biol Cell ; 15(11): 4971-89, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15371545

ABSTRACT

Bud growth in yeast is guided by myosin-driven delivery of secretory vesicles from the mother cell to the bud. We find transport occurs along two sets of actin cables assembled by two formin isoforms. The Bnr1p formin assembles cables that radiate from the bud neck into the mother, providing a stable mother-bud axis. These cables also depend on septins at the neck and are required for efficient transport from the mother to the bud. The Bni1p formin assembles cables that line the bud cortex and target vesicles to varying locations in the bud. Loss of these cables results in morphological defects as vesicles accumulate at the neck. Assembly of these cables depends on continued polarized secretion, suggesting vesicular transport provides a positive feedback signal for Bni1p activation, possibly by rho-proteins. By coupling different formin isoforms to unique cortical landmarks, yeast uses common cytoskeletal elements to maintain stable and dynamic axes in the same cell.


Subject(s)
Cytoskeletal Proteins/physiology , Microfilament Proteins/physiology , Saccharomyces cerevisiae Proteins/physiology , Saccharomyces cerevisiae/physiology , Actins/chemistry , Biological Transport , Body Patterning , Cytoskeleton/metabolism , Genotype , Glutathione Transferase/metabolism , Myosin Type V/chemistry , Plasmids/metabolism , Protein Isoforms , Pyrenes/chemistry , Recombinant Proteins/chemistry , Saccharomyces cerevisiae Proteins/chemistry , Temperature , Time Factors
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