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1.
J Cell Sci ; 132(22)2019 11 14.
Article in English | MEDLINE | ID: mdl-31636114

ABSTRACT

Cajal bodies are nuclear organelles involved in the nuclear phase of small nuclear ribonucleoprotein (snRNP) biogenesis. In this study, we identified the splicing factor TCERG1 as a coilin-associated factor that is essential for Cajal body integrity. Knockdown of TCERG1 disrupts the localization of the components of Cajal bodies, including coilin and NOLC1, with coilin being dispersed in the nucleoplasm into numerous small foci, without affecting speckles, gems or the histone locus body. Furthermore, the depletion of TCERG1 affects the recruitment of Sm proteins to uridine-rich small nuclear RNAs (snRNAs) to form the mature core snRNP. Taken together, the results of this study suggest that TCERG1 plays an important role in Cajal body formation and snRNP biogenesis.


Subject(s)
Coiled Bodies/physiology , RNA Splicing Factors/genetics , Ribonucleoproteins, Small Nuclear/metabolism , Transcriptional Elongation Factors/genetics , Humans , RNA Splicing , Ribonucleoproteins, Small Nuclear/genetics , Transcriptional Elongation Factors/metabolism
3.
Nucleic Acids Res ; 43(1): 385-95, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25477378

ABSTRACT

The RNA component of human telomerase (hTR) localizes to Cajal bodies, and it has been proposed that Cajal bodies play a role in the assembly of telomerase holoenzyme and telomerase trafficking. Here, the role of Cajal bodies was examined in Human cells deficient of coilin (i.e. coilin-knockout (KO) cells), in which no Cajal bodies are detected. In coilin-KO cells, a normal level of telomerase activity is detected and interactions between core factors of holoenzyme are preserved, indicating that telomerase assembly occurs in the absence of Cajal bodies. Moreover, dispersed hTR aggregates and forms foci specifically during S and G2 phase in coilin-KO cells. Colocalization of these hTR foci with telomeres implies proper telomerase trafficking, independent of Cajal bodies. Therefore, telomerase adds similar numbers of TTAGGG repeats to telomeres in coilin-KO and controls cells. Overexpression of TPP1-OB-fold blocks cell cycle-dependent formation of hTR foci and inhibits telomere extension. These findings suggest that telomerase assembly, trafficking and extension occur with normal efficiency in Cajal bodies deficient human cells. Thus, Cajal bodies, as such, are not essential in these processes, although it remains possible that non-coilin components of Cajal bodies and/or telomere binding proteins (e.g. TPP1) do play roles in telomerase biogenesis and telomere homeostasis.


Subject(s)
Coiled Bodies/physiology , Nuclear Proteins/physiology , Telomerase/metabolism , Telomere Homeostasis , Humans , Molecular Chaperones , Mutagenesis , Nuclear Proteins/genetics , S Phase/genetics , Shelterin Complex , Telomere/enzymology , Telomere-Binding Proteins/metabolism
4.
Exp Cell Res ; 319(3): 161-72, 2013 Feb 01.
Article in English | MEDLINE | ID: mdl-23059369

ABSTRACT

HHARI (also known as ARIH1) is an ubiquitin-protein ligase and is the cognate of the E2, UbcH7 (UBE2L3). To establish a functional role for HHARI in cellular proliferation processes, we performed a reverse genetics screen that identified n=86/522 (16.5%) ubiquitin conjugation components that have a statistically significant effect on cell proliferation, which included HHARI as a strong hit. We then produced and validated a panel of specific antibodies that establish HHARI as both a nuclear and cytoplasmic protein that is expressed in all cell types studied. HHARI was expressed at higher levels in nuclei, and co-localized with nuclear bodies including Cajal bodies (p80 coilin, NOPP140), PML and SC35 bodies. We confirmed reduced cellular proliferation after ARIH1 knockdown with individual siRNA duplexes, in addition to significantly increased levels of apoptosis, an increased proportion of cells in G2 phase of the cell cycle, and significant reductions in total cellular RNA levels. In head and neck squamous cell carcinoma biopsies, there are higher levels of HHARI expression associated with increased levels of proliferation, compared to healthy control tissues. We demonstrate that HHARI is associated with cellular proliferation, which may be mediated through its interaction with UbcH7 and modification of proteins in nuclear bodies.


Subject(s)
Biomarkers , Carrier Proteins/metabolism , Carrier Proteins/physiology , Cell Proliferation , Coiled Bodies/metabolism , Animals , Biomarkers/metabolism , Carrier Proteins/genetics , Cell Nucleus/metabolism , Cell Nucleus/physiology , Cell Nucleus/ultrastructure , Cells, Cultured , Coiled Bodies/physiology , Drosophila/genetics , Drosophila Proteins/genetics , HEK293 Cells , HeLa Cells , Humans , Mice , Protein Binding , Sequence Homology , Ubiquitin-Protein Ligases
5.
PLoS Biol ; 8(11): e1000521, 2010 Nov 02.
Article in English | MEDLINE | ID: mdl-21072240

ABSTRACT

The WRAP53 gene gives rise to a p53 antisense transcript that regulates p53. This gene also encodes a protein that directs small Cajal body-specific RNAs to Cajal bodies. Cajal bodies are nuclear organelles involved in diverse functions such as processing ribonucleoproteins important for splicing. Here we identify the WRAP53 protein as an essential factor for Cajal body maintenance and for directing the survival of motor neuron (SMN) complex to Cajal bodies. By RNA interference and immunofluorescence we show that Cajal bodies collapse without WRAP53 and that new Cajal bodies cannot be formed. By immunoprecipitation we find that WRAP53 associates with the Cajal body marker coilin, the splicing regulatory protein SMN, and the nuclear import receptor importinß, and that WRAP53 is essential for complex formation between SMN-coilin and SMN-importinß. Furthermore, depletion of WRAP53 leads to accumulation of SMN in the cytoplasm and prevents the SMN complex from reaching Cajal bodies. Thus, WRAP53 mediates the interaction between SMN and associated proteins, which is important for nuclear targeting of SMN and the subsequent localization of the SMN complex to Cajal bodies. Moreover, we detect reduced WRAP53-SMN binding in patients with spinal muscular atrophy, which is the leading genetic cause of infant mortality worldwide, caused by mutations in SMN1. This suggests that loss of WRAP53-mediated SMN trafficking contributes to spinal muscular atrophy.


Subject(s)
Cell Survival/physiology , Coiled Bodies/physiology , Motor Neurons/cytology , Telomerase/physiology , Cell Line , Humans , Molecular Chaperones , Muscular Atrophy, Spinal/metabolism , SMN Complex Proteins/metabolism
6.
Bioessays ; 32(12): 1077-89, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20954180

ABSTRACT

Gemins 2-8 and Unr-interacting protein (UNRIP) are intimate partners of the survival motor neuron (SMN) protein, which is the determining factor for the neuromuscular disorder spinal muscular atrophy (SMA). The most documented role of SMN, Gemins and UNRIP occurs within the large macromolecular SMN complex and involves the cytoplasmic assembly of spliceosomal uridine-rich small nuclear ribonucleoproteins (UsnRNPs), a housekeeping process critical in all cells. Several reports detailing alternative functions for SMN in either motor neurons or skeletal muscles may, however, hold the answer to the extreme neuromuscular tissue specificity observed in SMA. Recent discoveries indicate that collaboration between SMN and Gemins also extends to these non-canonical functions, hence raising the possibility that mutations in Gemin genes may be the cause of unlinked neuromuscular hereditary syndromes. This review evaluates the functions of Gemins and UNRIP inside the SMN complex and discusses whether these less notorious SMN complex members are capable of acting independently of SMN.


Subject(s)
Muscular Atrophy, Spinal/genetics , Muscular Atrophy, Spinal/metabolism , Ribonucleoproteins, Small Nuclear/chemistry , Ribonucleoproteins, Small Nuclear/metabolism , SMN Complex Proteins/chemistry , SMN Complex Proteins/metabolism , Animals , Coiled Bodies/physiology , Humans , Motor Neurons/physiology , Muscle, Skeletal/physiology , SMN Complex Proteins/genetics , Spliceosomes
7.
Biochem Soc Trans ; 38(2): 672-6, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20298241

ABSTRACT

The snoRNAs (small nucleolar RNAs) and related scaRNAs (small RNAs in the Cajal bodies) represent a major class of nuclear RNAs that guide 2'-O-ribose methylation and pseudouridylation of rRNAs, snRNAs (small nuclear RNAs) and other RNA targets. In vivo, all snoRNAs associate with a set of four highly conserved nucleolar proteins, forming the functional snoRNPs (small nucleolar ribonucleoproteins). The core structure of these mature snoRNPs has now been well described in eukaryotes, but less is known of their biogenesis. Recent data in animals and yeast reveal that assembly of the snoRNPs is a complex process that implicates several auxiliary proteins and transient protein-protein interactions. This new level of snoRNP regulation is now beginning to be unravelled in animals and yeast, but remains unexplored in plants. In the present paper, we review recent data from genomic and functional analysis allowing the identification and study of factors controlling the biogenesis of plant snoRNPs and their impact on plant development.


Subject(s)
Plants/genetics , Ribonucleoproteins, Small Nucleolar/genetics , Ribonucleoproteins, Small Nucleolar/physiology , Animals , Cell Nucleolus/genetics , Cell Nucleolus/metabolism , Coiled Bodies/metabolism , Coiled Bodies/physiology , Conserved Sequence , Genetic Variation , Models, Biological , Plants/metabolism , Ribonucleoproteins, Small Nucleolar/metabolism
8.
Arch Biochem Biophys ; 496(2): 69-76, 2010 Apr 15.
Article in English | MEDLINE | ID: mdl-20193656

ABSTRACT

The Cajal body (CB) is a subnuclear domain that contains proteins and factors involved in a diverse range of activities including ribonucleoprotein maturation, histone gene transcription and telomerase assembly. Among these activities, the CBs' role in small nuclear ribonucleoprotein (snRNP) biogenesis is best characterized. Although CBs are found in plants, flies and mammals, not all cell types contain CBs. Rather, CBs are most prominent in transcriptionally active cells, such as cancer and neuronal cells. Many CB components, including the CB marker protein coilin, are phosphorylated in humans. The functional consequence of phosphorylation on CB assembly, activity and disassembly is largely unknown. Also unknown are the signaling pathways, kinases and phosphatases that act upon proteins which localize in the CB. The goal of this review is to demonstrate the need for a concerted effort towards elucidating the functional consequence of phosphorylation on CB formation and activity.


Subject(s)
Coiled Bodies/physiology , Ribonucleoproteins, Small Nuclear/metabolism , Signal Transduction/physiology , Models, Biological , Phosphorylation
9.
Proc Natl Acad Sci U S A ; 106(31): 12747-52, 2009 Aug 04.
Article in English | MEDLINE | ID: mdl-19617559

ABSTRACT

Nuclear bodies are distinct subnuclear structures. The survival of motoneuron (SMN) gene is mutated or deleted in patients with the neurodegenerative disease spinal muscular atrophy (SMA). The gene product SMN is a marker protein for one class of nuclear bodies denoted as nuclear gems. SMN has also been found in Cajal bodies, which co-localize with gems in many cell types. Interestingly, SMA patients display a reduced number of gems. Little is known about the regulation of nuclear body formation and stabilization. We have previously shown that a nuclear isoform of the fibroblast growth factor-2 (FGF-2(23)) binds directly to SMN. In this study, we analyzed the consequences of FGF-2(23) binding to SMN with regard to nuclear body formation. On a molecular level, we showed that FGF-2(23) competed with Gemin2 (a component of the SMN complex that is necessary for gem stabilization) for binding to SMN. Down-regulation of Gemin2 by siRNA caused destabilization of SMN-positive nuclear bodies. This process is reflected in both cellular and in vivo systems by a negative regulatory function of FGF-2 in nuclear body formation: in HEK293 cells, FGF-2(23) decreased the number of SMN-positive nuclear bodies. The same effect could be observed in motoneurons of FGF-2 transgenic mice. This study demonstrates the functional role of a growth factor in the regulation of structural entities of the nucleus.


Subject(s)
Coiled Bodies/physiology , Fibroblast Growth Factor 2/physiology , Gemini of Coiled Bodies/physiology , Animals , Humans , Immunoprecipitation , Mice , Mice, Transgenic , Nerve Tissue Proteins/physiology , RNA-Binding Proteins/physiology , Receptor, Fibroblast Growth Factor, Type 1/physiology , SMN Complex Proteins/analysis , SMN Complex Proteins/physiology
11.
J Cell Mol Med ; 12(2): 471-8, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18266958

ABSTRACT

The Interstitial Cells of Cajal (ICC) are responsible for rhythmic electrical activity. A paralytic ileus is present in gastroschisis (GS), a malformation due to a defective closure of the abdominal wall through which part of the intestine herniates during pregnancy. In experimental GS, ICC morphological immaturity was shown in the rat foetus at-term but it could not be demonstrated whether differentiation is accomplished post-natally. For this purpose we morphologically investigated ICC, as well as enteric neurons and smooth muscle cells, in a case of human GS at birth and 1 month later when peristaltic activity had initiated. A 36 weeks gestation female was born by c/section with prenatal diagnosis of GS and possible volvulus of the herniated intestine. At birth, the necrotic intestine was resected and both ileostomy and colostomy were performed. The intestine continuity was restored after 4 weeks. Intestinal specimens, taken during both operations at the level of the proximal stoma, were immunostained with c-kit, neuron-specific-enolase and alpha-smooth-muscle-actin antibodies and some processed for electron microscopy. ICC were present at the myenteric plexus only. At birth, these cells were rare and ultrastructurally immature; 1 month later, when partial enteral feeding was tolerated, they formed rows or groups and many of them were ultrastructurally differentiated. Neurons and smooth muscle cells, immature at birth, had developed after 1 month. Therefore, ICC differentiation, as well as that of neurons and smooth muscle cells, is delayed at birth and this might explain the paralytic ileus in GS. One month later, differentiation quickly proceeded at all cellular levels paralleling the increasing tolerance of enteral nutrition.


Subject(s)
Coiled Bodies/physiology , Fetus/cytology , Gastroschisis/embryology , Ileum/cytology , Ileum/growth & development , Coiled Bodies/enzymology , Coiled Bodies/metabolism , Coiled Bodies/ultrastructure , Colostomy , Enteric Nervous System/cytology , Enteric Nervous System/enzymology , Enteric Nervous System/ultrastructure , Female , Fetus/enzymology , Follow-Up Studies , Humans , Ileostomy , Ileum/enzymology , Ileum/surgery , Ileum/ultrastructure , Immunohistochemistry , Infant, Newborn , Myenteric Plexus/cytology , Myenteric Plexus/enzymology , Myenteric Plexus/ultrastructure , Myocytes, Smooth Muscle/ultrastructure , Neurons/cytology , Neurons/enzymology , Neurons/ultrastructure , Parenteral Nutrition , Phosphopyruvate Hydratase/metabolism , Pregnancy , Proto-Oncogene Proteins c-kit/metabolism , Time Factors , Treatment Outcome
12.
Neurogastroenterol Motil ; 20(1): 69-79, 2008 Jan.
Article in English | MEDLINE | ID: mdl-17931338

ABSTRACT

To assess whether afferent vagal intramuscular arrays (IMAs), putative gastrointestinal mechanoreceptors, form contacts with interstitial cells of Cajal of the intramuscular type (ICC-IM) and to describe any such contacts, electron microscopic analyses were performed on the external muscle layers of the fundus containing dextran-labelled diaminobenzidin (DAB)-stained IMAs. Special staining and embedding techniques were developed to preserve ultrastructural features. Within the muscle layers, IMA varicosities were observed in nerve bundles traversing major septa without contact with ICC-IM, contacting unlabelled neurites and glial cells. IMA varicosities were encountered in minor septa in contact with ICC-IM which were not necessarily in close contact with muscle cells. In addition, IMA varicosities were observed within muscle bundles in close contact with ICC-IM which were in gap junction contact with muscle cells. IMAs formed varicosities containing predominantly small agranular vesicles, occasionally large granular vesicles and prejunctional thickenings in apposition to ICC-IM processes, indicating communication between ICC and IMA via synapse-like contacts. Taken together, these different morphological features are consistent with a hypothesized mechanoreceptor role for IMA-ICC complexes. Intraganglionic laminar ending varicosities contacted neuronal somata and dendrites in the myenteric plexus of the fundus, but no contacts with ICC associated with Auerbach's plexus were encountered.


Subject(s)
Coiled Bodies/physiology , Gastric Fundus/physiology , Mechanoreceptors/physiology , Vagus Nerve/physiology , Afferent Pathways/physiology , Animals , Gastric Fundus/innervation , Male , Muscle, Smooth/cytology , Muscle, Smooth/physiology , Rats , Rats, Sprague-Dawley
13.
J Cell Biol ; 179(6): 1095-103, 2007 Dec 17.
Article in English | MEDLINE | ID: mdl-18070915

ABSTRACT

Although bulk chromatin is thought to have limited mobility within the interphase eukaryotic nucleus, directed long-distance chromosome movements are not unknown. Cajal bodies (CBs) are nuclear suborganelles that nonrandomly associate with small nuclear RNA (snRNA) and histone gene loci in human cells during interphase. However, the mechanism responsible for this association is uncertain. In this study, we present an experimental system to probe the dynamic interplay of CBs with a U2 snRNA target gene locus during transcriptional activation in living cells. Simultaneous four-dimensional tracking of CBs and U2 genes reveals that target loci are recruited toward relatively stably positioned CBs by long-range chromosomal motion. In the presence of a dominant-negative mutant of beta-actin, the repositioning of activated U2 genes is markedly inhibited. This supports a model in which nuclear actin is required for these rapid, long-range chromosomal movements.


Subject(s)
Actins/physiology , Chromosomes/physiology , Coiled Bodies/physiology , RNA, Small Nuclear/metabolism , Actins/metabolism , Chromosomes/metabolism , Chromosomes/ultrastructure , Coiled Bodies/metabolism , Coiled Bodies/ultrastructure , Genes, Reporter , HeLa Cells , Humans , Luminescent Proteins/analysis , Recombinant Fusion Proteins/analysis , Transcriptional Activation
14.
J Cell Biol ; 179(6): 1093-4, 2007 Dec 17.
Article in English | MEDLINE | ID: mdl-18070916

ABSTRACT

Recent progress in live cell imaging suggests a role for nuclear actin in chromatin movement. In this issue, for the first time, a gene locus moving toward a subnuclear compartment was tracked. Motion of the locus is actin dependent, raising the question of whether chromatin movements are random or directed.


Subject(s)
Cell Nucleus/metabolism , Chromatin/metabolism , Coiled Bodies/physiology , Models, Genetic , Actins/physiology , Cell Compartmentation , Cell Nucleus Structures , Chromatin/physiology , Chromosomes/metabolism , Chromosomes/physiology , Coiled Bodies/metabolism , HeLa Cells , Humans
15.
Biochem Biophys Res Commun ; 360(1): 40-5, 2007 Aug 17.
Article in English | MEDLINE | ID: mdl-17588531

ABSTRACT

Cajal bodies (CBs) are small mobile organelles found throughout the nucleoplasm of animal and plant cells. The dynamics of these organelles involves interactions with the nucleolus. The later has been found to play a substantial role in the compensatory response that evolved in eurythermal fish to adapt to the cyclic seasonal habitat changes, i.e., temperature and photoperiod. Contrary to being constitutive, rRNA synthesis is dramatically regulated between summer and winter, thus affecting ribosomal biogenesis which plays a central role in the acclimatization process. To examine whether CBs, up to now, never described in fish, were also sustaining the phenotypic plasticity observed in nuclei of fish undergoing seasonal acclimatization, we identified these organelles both, by transmission electronic microscopy and immunodetection with the marker protein p80-coilin. We found transcripts in all tissues analyzed. Furthermore we assessed that p80-coilin gene expression was always higher in summer-acclimatized fish when compared to that adapted to the cold season, indicating that p80-coilin expression is modulated upon seasonal acclimatization. Concurrently, CBs were more frequently found in summer-acclimatized carp which suggests that the organization of CBs is involved in adaptive processes and contribute to the phenotypic plasticity of fish cell nuclei observed concomitantly with profound reprogramming of nucleolar components and regulation of ribosomal rRNAs.


Subject(s)
Acclimatization/physiology , Carps/physiology , Cell Nucleus/physiology , Coiled Bodies/physiology , Nuclear Proteins/metabolism , RNA, Ribosomal/metabolism , Animals , Male , Nuclear Proteins/genetics , Phenotype , Protein Biosynthesis/physiology
16.
Ann Biomed Eng ; 35(9): 1595-607, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17486452

ABSTRACT

A physiologically realistic quantitative description of the electrical behavior of a gastric smooth muscle (SM) cell is presented. The model describes the response of a SM cell when activated by an electrical stimulus coming from the network of interstitial cells of Cajal (ICC) and is mediated by the activation of different ion channels species in the plasma membrane. The conductances (predominantly Ca2+ and K+) that are believed to substantially contribute to the membrane potential fluctuations during slow wave activity have been included in the model. A phenomenological description of intracellular Ca2+ dynamics has also been included because of its primary importance in regulating a number of cellular processes. In terms of shape, duration, and amplitude, the resulting simulated smooth muscle depolarizations (SMDs) are in good agreement with experimentally recordings from mammalian gastric SM in control and altered conditions. This model has also been designed to be suitable for incorporation into large scale multicellular simulations.


Subject(s)
Models, Biological , Muscle, Smooth/physiology , Stomach/cytology , Stomach/physiology , Animals , Calcium Channels/physiology , Cell Membrane/chemistry , Coiled Bodies/physiology , Computer Simulation , Electric Stimulation/methods , Electrophysiology , Membrane Potentials/physiology , Potassium Channels/physiology
17.
Neurogastroenterol Motil ; 19(4): 245-52, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17391240

ABSTRACT

Normal gastrointestinal (GI) motility is required to mix digestive enzymes and food and to move content along the GI tract. Underlying the complex motor patterns of the gut are electrical events that reflect ion flux across cell membranes. Smooth muscle electrical activity is directly influenced by GI interstitial cells of Cajal, whose rhythmic oscillations in membrane potential in part determine the excitability of GI smooth muscle and its response to neuronal input. Coordinated activity of the ion channels responsible for the conductances that underlie ion flux in both smooth muscle and interstitial cells is a requisite for normal motility. These conductances are regulated by many factors, including mechanical stress. Recent studies have revealed mechanosensitivity at the level of the ion channels, and the mechanosensor within the channel has been identified in many cases. This has led to better comprehension of the role of mechanosensitive conductances in normal physiology and will undoubtedly lead to understanding of the consequences of disturbances in these conductances.


Subject(s)
Coiled Bodies/physiology , Gastrointestinal Tract/physiology , Ion Channels/physiology , Muscle, Smooth/physiology , Calcium Channels/physiology , Food , Gastrointestinal Transit , Humans , Mechanoreceptors/physiology , Mechanotransduction, Cellular/physiology , Potassium Channels/physiology , Sodium Channels/physiology
18.
Pathologe ; 28(2): 143-8, 2007 Mar.
Article in German | MEDLINE | ID: mdl-17294155

ABSTRACT

Intestinal innervation disorders are part of the broad etiological spectrum of chronic constipation and need to be specifically addressed in differential diagnosis. The enteric nervous system constitutes the largest peripheral nervous system of its own ("brain in the gut"), and is involved in the mediation of intestinal motility. Morphologically different nerve cell types aggregate into intramural plexus layers and release a multitude of neurotransmitters. Malformations or lesions of the enteric nervous system may lead to a severely prolonged intestinal transit time resulting in chronic constipation resistant to conservative treatment. In contrast to the early manifestation of aganglionosis, non-aganglionic or acquired alterations to the intramural nerve plexus often remain unrecognised up to adulthood. Histopathological diagnosis is carried out by enzyme or immunohistochemical staining, either on sections or whole mount preparations, allowing an optimal visualization of the nerve plexus architecture. To diagnose hypoganglionosis, enteric ganglionitis or alterations in interstitial cells of Cajal, full-thickness biopsies are required. Interstitial cells of Cajal contribute significantly to the mediation of intestinal motility by generating "slow wave" activity. In adult patients with slow-transit constipation and megacolon, the intramuscular networks of the interstitial cells of Cajal show a significantly reduced density.


Subject(s)
Coiled Bodies/pathology , Constipation/pathology , Enteric Nervous System/pathology , Adult , Brain/physiopathology , Chronic Disease , Coiled Bodies/physiology , Constipation/diagnosis , Diagnosis, Differential , Enteric Nervous System/physiology , Gastrointestinal Motility/physiology , Humans
19.
Cell Mol Life Sci ; 64(5): 581-8, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17256087

ABSTRACT

As the site of gene expression and regulation, the nucleus is the control center of the cell. It might be thought that degradation of nuclear contents is strictly 'off-limits,' given the importance of the genetic information contained within the nucleus, but it has recently been reported that partial degradation of the nucleus may occur in yeast. Here we summarize the evidence for the degradation and quality control of proteins found with the nucleus and its compartments, and of nucleic acids that may occur under certain specific conditions. Only under certain special conditions such as differentiation of the lens are the entire nuclear contents degraded.


Subject(s)
Cell Nucleus/physiology , Gene Expression Regulation , Animals , Autophagy , Cell Nucleolus/physiology , Cell Nucleus/genetics , Cell Physiological Phenomena , Coiled Bodies/physiology , DNA/metabolism , Genetic Diseases, Inborn/genetics , Humans , Nuclear Proteins/metabolism , Organelles/physiology
20.
J Cell Mol Med ; 10(2): 280-91, 2006.
Article in English | MEDLINE | ID: mdl-16796799

ABSTRACT

The smooth muscle layer of the urethra generates spontaneous myogenic tone that is thought to make a major contribution to urinary continence. The mechanisms underlying generation of tone remain unclear, however recent studies from our laboratory highlighted a role for a specialised population of pacemaker cells which we originally referred to as interstitial cells (IC) and now term ICC. Urethra ICC possess an electrical pacemaker mechanism characterised by rhythmic activation of Ca(2+)-activated Cl(-) channels leading to spontaneous transient inward currents (STICs) under voltage clamp and spontaneous transient depolarisations (STDs) under current clamp conditions. Both STICS and STDs are now known to be associated with spontaneous Ca(2+) oscillations that result from a complex interplay between release of Ca(2+) from intracellular stores and Ca(2+) influx across the plasma membrane. In this review we will consider some of the precise mechanisms involved in the generation of pacemaker activity and discuss how these are modulated by excitatory and inhibitory neurotransmitters.


Subject(s)
Cell Biology/history , Coiled Bodies/metabolism , Muscle, Smooth/metabolism , Urethra/cytology , Animals , Calcium Signaling , Coiled Bodies/physiology , Forecasting , History, 20th Century , History, 21st Century , Muscle Contraction/drug effects , Muscle Contraction/physiology , Muscle, Smooth/cytology , Muscle, Smooth/physiology , Neurotransmitter Agents/classification , Neurotransmitter Agents/pharmacology , Patch-Clamp Techniques
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