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1.
EMBO J ; 41(21): e112107, 2022 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-36125182

RESUMO

Over the course of evolution, the centrosome function has been conserved in most eukaryotes, but its core architecture has evolved differently in some clades, with the presence of centrioles in humans and a spindle pole body (SPB) in yeast. Similarly, the composition of these two core elements has diverged, with the exception of Centrin and SFI1, which form a complex in yeast to initiate SPB duplication. However, it remains unclear whether this complex exists at centrioles and whether its function has been conserved. Here, using expansion microscopy, we demonstrate that human SFI1 is a centriolar protein that associates with a pool of Centrin at the distal end of the centriole. We also find that both proteins are recruited early during procentriole assembly and that depletion of SFI1 results in the loss of the distal pool of Centrin, without altering centriole duplication. Instead, we show that SFI1/Centrin complex is essential for centriolar architecture, CEP164 distribution, and CP110 removal during ciliogenesis. Together, our work reveals a conserved SFI1/Centrin module displaying divergent functions between mammals and yeast.


Assuntos
Proteínas de Ligação ao Cálcio , Proteínas de Ciclo Celular , Centríolos , Animais , Humanos , Proteínas de Ciclo Celular/metabolismo , Centríolos/metabolismo , Proteínas Repressoras/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Corpos Polares do Fuso/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo
2.
Open Biol ; 12(1): 210343, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35042404

RESUMO

Centrosomes are important organizers of microtubules within animal cells. They comprise a pair of centrioles surrounded by the pericentriolar material, which nucleates and organizes the microtubules. To maintain centrosome numbers, centrioles must duplicate once and only once per cell cycle. During S-phase, a single new 'daughter' centriole is built orthogonally on one side of each radially symmetric 'mother' centriole. Mis-regulation of duplication can result in the simultaneous formation of multiple daughter centrioles around a single mother centriole, leading to centrosome amplification, a hallmark of cancer. It remains unclear how a single duplication site is established. It also remains unknown whether this site is pre-defined or randomly positioned around the mother centriole. Here, we show that within Drosophila syncytial embryos daughter centrioles preferentially assemble on the side of the mother facing the nuclear envelope, to which the centrosomes are closely attached. This positional preference is established early during duplication and remains stable throughout daughter centriole assembly, but is lost in centrosomes forced to lose their connection to the nuclear envelope. This shows that non-centrosomal cues influence centriole duplication and raises the possibility that these external cues could help establish a single duplication site.


Assuntos
Centríolos , Proteínas de Drosophila , Animais , Centríolos/metabolismo , Centrossomo/metabolismo , Drosophila/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Membrana Nuclear/metabolismo
3.
Tunis Med ; 97(3): 508-511, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31729728

RESUMO

Atrioventricular block (AVB) during pregnancy is a rare situation. Women carriers of AVB support generally well pregnancy. Currently, there is no established consensus guiding peripartum management, and the course of action is guided by observational studies. We report the case of a parturient carrier of a congenital AVB discovered at the end of pregnancy.


Assuntos
Bloqueio Atrioventricular/diagnóstico , Complicações Cardiovasculares na Gravidez/diagnóstico , Adulto , Bloqueio Atrioventricular/terapia , Cesárea , Feminino , Humanos , Complicações do Trabalho de Parto/diagnóstico , Complicações do Trabalho de Parto/terapia , Gravidez , Complicações Cardiovasculares na Gravidez/terapia , Terceiro Trimestre da Gravidez , Diagnóstico Pré-Natal , Prova de Trabalho de Parto
4.
Methods Cell Biol ; 129: 383-392, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26175449

RESUMO

Like centrosomes, yeast spindle pole bodies (SPBs) undergo a tightly controlled duplication cycle in order to restrict their number to one or two per cell and promote the assembly of a bipolar spindle at mitotic entry. This conservative duplication cycle is tightly coordinated with cell cycle progression although the mechanisms that ensure this coordination remain largely unknown. In this chapter, we describe simple high resolution microscopy- and quantitative light microscopy-based methods that allow to monitor SPB biogenesis in fission yeast and may be useful to study the molecular pathways controlling the successive phases of the duplication cycle.


Assuntos
Schizosaccharomyces/fisiologia , Corpos Polares do Fuso/fisiologia , Microscopia de Fluorescência , Análise de Célula Única
5.
Mol Biol Cell ; 26(12): 2343-56, 2015 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-25904327

RESUMO

Nup98 is a glycine-leucine-phenylalanine-glycine (GLFG) repeat-containing nucleoporin that, in addition to nuclear transport, contributes to multiple aspects of gene regulation. Previous studies revealed its dynamic localization within intranuclear structures known as GLFG bodies. Here we show that the mammalian Nup107-160 complex (Y-complex), a major scaffold module of the nuclear pore, together with its partner Elys, colocalizes with Nup98 in GLFG bodies. The frequency and size of GLFG bodies vary among HeLa sublines, and we find that an increased level of Nup98 is associated with the presence of bodies. Recruitment of the Y-complex and Elys into GLFG bodies requires the C-terminal domain of Nup98. During cell division, Y-Nup-containing GLFG bodies are disassembled in mitotic prophase, significantly ahead of nuclear pore disassembly. FRAP studies revealed that, unlike at nuclear pores, the Y-complex shuttles into and out of GLFG bodies. Finally, we show that within the nucleoplasm, a fraction of Nup107, a key component of the Y-complex, displays reduced mobility, suggesting interaction with other nuclear components. Together our data uncover a previously neglected intranuclear pool of the Y-complex that may underscore a yet-uncharacterized function of these nucleoporins inside the nucleus, even in cells that contain no detectable GLFG bodies.


Assuntos
Núcleo Celular/metabolismo , Complexo de Proteínas Formadoras de Poros Nucleares/metabolismo , Proteínas Nucleares/metabolismo , Núcleo Celular/fisiologia , Proteínas de Ligação a DNA/metabolismo , Recuperação de Fluorescência Após Fotodegradação , Células HeLa , Humanos , Mitose , Fatores de Transcrição/metabolismo
6.
J Cell Sci ; 128(8): 1481-93, 2015 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-25736294

RESUMO

Spindle pole biogenesis and segregation are tightly coordinated to produce a bipolar mitotic spindle. In yeasts, the spindle pole body (SPB) half-bridge composed of Sfi1 and Cdc31 duplicates to promote the biogenesis of a second SPB. Sfi1 accumulates at the half-bridge in two phases in Schizosaccharomyces pombe, from anaphase to early septation and throughout G2 phase. We found that the function of Sfi1-Cdc31 in SPB duplication is accomplished before septation ends and G2 accumulation starts. Thus, Sfi1 early accumulation at mitotic exit might correspond to half-bridge duplication. We further show that Cdc31 phosphorylation on serine 15 in a Cdk1 (encoded by cdc2) consensus site is required for the dissociation of a significant pool of Sfi1 from the bridge and timely segregation of SPBs at mitotic onset. This suggests that the Cdc31 N-terminus modulates the stability of Sfi1-Cdc31 arrays in fission yeast, and impacts on the timing of establishment of spindle bipolarity.


Assuntos
Proteínas de Ligação ao Cálcio/fisiologia , Proteínas de Ligação a Calmodulina/fisiologia , Pontos de Checagem do Ciclo Celular , Proteínas de Ciclo Celular/fisiologia , Proteínas de Schizosaccharomyces pombe/fisiologia , Schizosaccharomyces/citologia , Corpos Polares do Fuso/fisiologia , Proteína Quinase CDC2/fisiologia , Citocinese , Mitose
7.
Cancer Res ; 73(9): 2905-15, 2013 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-23396587

RESUMO

Metastasis, a fatal complication of breast cancer, does not fully benefit from available therapies. In this study, we investigated whether ATIP3, the major product of 8p22 MTUS1 gene, may be a novel biomarker and therapeutic target for metastatic breast tumors. We show that ATIP3 is a prognostic marker for overall survival among patients with breast cancer. Notably, among metastatic tumors, low ATIP3 levels associate with decreased survival of the patients. By using a well-defined experimental mouse model of cancer metastasis, we show that ATIP3 expression delays the time-course of metastatic progression and limits the number and size of metastases in vivo. In functional studies, ATIP3 silencing increases breast cancer cell migration, whereas ATIP3 expression significantly reduces cell motility and directionality. We report here that ATIP3 is a potent microtubule-stabilizing protein whose depletion increases microtubule dynamics. Our data support the notion that by decreasing microtubule dynamics, ATIP3 controls the ability of microtubule tips to reach the cell cortex during migration, a mechanism that may account for reduced cancer cell motility and metastasis. Of interest, we identify a functional ATIP3 domain that associates with microtubules and recapitulates the effects of ATIP3 on microtubule dynamics, cell proliferation, and migration. Our study is a major step toward the development of new personalized treatments against metastatic breast tumors that have lost ATIP3 expression.


Assuntos
Neoplasias da Mama/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Animais , Neoplasias da Mama/patologia , Adesão Celular , Linhagem Celular Tumoral , Movimento Celular , Modelos Animais de Doenças , Progressão da Doença , Feminino , Humanos , Camundongos , Microscopia de Fluorescência/métodos , Microtúbulos/metabolismo , Metástase Neoplásica , Análise de Sequência com Séries de Oligonucleotídeos , Plasmídeos/metabolismo , Prognóstico , Estrutura Terciária de Proteína , Resultado do Tratamento
8.
J Cell Biol ; 192(5): 855-71, 2011 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-21383080

RESUMO

Centrosomes are closely associated with the nuclear envelope (NE) throughout the cell cycle and this association is maintained in prophase when they separate to establish the future mitotic spindle. At this stage, the kinetochore constituents CENP-F, NudE, NudEL, dynein, and dynactin accumulate at the NE. We demonstrate here that the N-terminal domain of the nuclear pore complex (NPC) protein Nup133, although largely dispensable for NPC assembly, is required for efficient anchoring of the dynein/dynactin complex to the NE in prophase. Nup133 exerts this function through an interaction network via CENP-F and NudE/EL. We show that this molecular chain is critical for maintaining centrosome association with the NE at mitotic entry and contributes to this process without interfering with the previously described RanBP2-BICD2-dependent pathway of centrosome anchoring. Finally, our study reveals that tethering of centrosomes to the nuclear surface at the G2/M transition contributes, along with other cellular mechanisms, to early stages of bipolar spindle assembly.


Assuntos
Centrossomo/metabolismo , Membrana Nuclear/metabolismo , Complexo de Proteínas Formadoras de Poros Nucleares/fisiologia , Poro Nuclear/metabolismo , Prófase , Proteínas de Transporte/metabolismo , Proteínas de Transporte/fisiologia , Linhagem Celular Tumoral , Polaridade Celular , Centrossomo/ultraestrutura , Proteínas Cromossômicas não Histona/metabolismo , Proteínas Cromossômicas não Histona/fisiologia , Complexo Dinactina , Dineínas/metabolismo , Células HeLa , Humanos , Espaço Intranuclear/metabolismo , Espaço Intranuclear/ultraestrutura , Proteínas dos Microfilamentos/metabolismo , Proteínas dos Microfilamentos/fisiologia , Proteínas Associadas aos Microtúbulos/metabolismo , Antígenos de Histocompatibilidade Menor , Membrana Nuclear/ultraestrutura , Complexo de Proteínas Formadoras de Poros Nucleares/química , Complexo de Proteínas Formadoras de Poros Nucleares/metabolismo , Mapeamento de Interação de Proteínas , Fuso Acromático/metabolismo
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