SFI1 and centrin form a distal end complex critical for proper centriole architecture and ciliogenesis

2021 ◽  
Author(s):  
Imène B. Bouhlel ◽  
Marine. H. Laporte ◽  
Eloïse Bertiaux ◽  
Alexia Giroud ◽  
Susanne Borgers ◽  
...  
Keyword(s):  
Basal Body ◽  
Spindle Pole Body ◽  
Super Resolution ◽  
Spindle Pole ◽  
Specific Loss ◽  
Centriole Duplication ◽  
Pole Body ◽  
Core Elements ◽  
Bona Fide ◽  
And Function

AbstractOver the course of evolution, the function of the centrosome has been conserved in most eukaryotes, but its core architecture has evolved differently in some clades, as illustrated by the presence of centrioles in humans and a spindle pole body in yeast (SPB). Consistently, the composition of these two core elements has diverged greatly, with the exception of centrin, a protein known to form a complex with Sfi1 in yeast to structurally initiate SPB duplication. Even though SFI1 has been localized to human centrosomes, whether this complex exists at centrioles and whether its function has been conserved is still unclear. Here, using conventional fluorescence and super-resolution microscopies, we demonstrate that human SFI1 is a bona fide centriolar protein localizing to the very distal end of the centriole, where it associates with a pool of distal centrin. We also found that both proteins are recruited early during procentriole assembly and that depletion of SFI1 results in the specific loss of the distal pool of centrin, without altering centriole duplication in human cells, in contrast to its function for SPB. Instead, we found that SFI1/centrin complexes are essential for correct centriolar architecture as well as for ciliogenesis. We propose that SFI1/centrin complexes may guide centriole growth to ensure centriole integrity and function as a basal body.

scholarly journals BIK1, a protein required for microtubule function during mating and mitosis in Saccharomyces cerevisiae, colocalizes with tubulin.

1990 ◽  
Vol 111 (6) ◽  
pp. 2573-2586 ◽  
Author(s):  
V Berlin ◽  
C A Styles ◽  
G R Fink
Keyword(s):  
Synthetic Lethality ◽  
Nuclear Fusion ◽  
Spindle Pole Body ◽  
Spindle Pole ◽  
Microtubule Assembly ◽  
Chromosome Loss ◽  
Physical Interaction ◽  
Pole Body ◽  
Cytoplasmic Microtubules ◽  
And Function

BIK1 function is required for nuclear fusion, chromosome disjunction, and nuclear segregation during mitosis. The BIK1 protein colocalizes with tubulin to the spindle pole body and mitotic spindle. Synthetic lethality observed in double mutant strains containing a mutation in the BIK1 gene and in the gene for alpha- or beta-tubulin is consistent with a physical interaction between BIK1 and tubulin. Furthermore, over- or underexpression of BIK1 causes aberrant microtubule assembly and function, bik1 null mutants are viable but contain very short or undetectable cytoplasmic microtubules. Spindle formation often occurs strictly within the mother cell, probably accounting for the many multinucleate and anucleate bik1 cells. Elevated levels of chromosome loss in bik1 cells are indicative of defective spindle function. Nuclear fusion is blocked in bik1 x bik1 zygotes, which have truncated cytoplasmic microtubules. Cells overexpressing BIK1 initially have abnormally short or nonexistent spindle microtubules and long cytoplasmic microtubules. Subsequently, cells lose all microtubule structures, coincident with the arrest of division. Based on these results, we propose that BIK1 is required stoichiometrically for the formation or stabilization of microtubules during mitosis and for spindle pole body fusion during conjugation.

scholarly journals HIV-1 Vpr Induces Defects in Mitosis, Cytokinesis, Nuclear Structure, and Centrosomes

2004 ◽  
Vol 15 (4) ◽  
pp. 1793-1801 ◽  
Author(s):  
Fred Chang ◽  
Fabio Re ◽  
Sarah Sebastian ◽  
Shelley Sazer ◽  
Jeremy Luban
Keyword(s):  
Fission Yeast ◽  
Cell Cycle Progression ◽  
Spindle Pole Body ◽  
Spindle Pole ◽  
Human Cells ◽  
Yeast Cells ◽  
M Cell ◽  
Pole Body ◽  
And Function ◽  
Hiv 1

Human immunodeficiency virus type 1 (HIV-1) Vpr is a 15-kDa accessory protein that contributes to several steps in the viral replication cycle and promotes virus-associated pathology. Previous studies demonstrated that Vpr inhibits G2/M cell cycle progression in both human cells and in the fission yeast Schizosaccharomyces pombe. Here, we report that, upon induction of vpr expression, fission yeast exhibited numerous defects in the assembly and function of the mitotic spindle. In particular, two spindle pole body proteins, sad1p and the polo kinase plo1p, were delocalized in vpr-expressing yeast cells, suggesting that spindle pole body integrity was perturbed. In addition, nuclear envelope structure, contractile actin ring formation, and cytokinesis were also disrupted. Similar Vpr-induced defects in mitosis and cytokinesis were observed in human cells, including aberrant mitotic spindles, multiple centrosomes, and multinucleate cells. These defects in cell division and centrosomes might account for some of the pathological effects associated with HIV-1 infection.

scholarly journals Direct experimental evidence for the existence, structural basis and function of astral forces during anaphase B in vivo

1991 ◽  
Vol 100 (2) ◽  
pp. 279-288 ◽  
Author(s):  
J.R. Aist ◽  
C.J. Bayles ◽  
W. Tao ◽  
M.W. Berns
Keyword(s):  
Critical Mass ◽  
Spindle Pole Body ◽  
Spindle Pole ◽  
Structural Basis ◽  
Mitotic Apparatus ◽  
Pole Body ◽  
Spindle Microtubules ◽  
Spindle Elongation ◽  
And Function ◽  
Anaphase B

The existence, structural basis and function of astral forces that are active during anaphase B in the fungus, Nectria haematococca, were revealed by experiments performed on living cells. When one of the two asters of a mitotic apparatus was damaged, the entire mitotic apparatus migrated rapidly in the direction of the opposing astral forces, showing that the force that accelerated spindle pole body separation in earlier experiments is located in the asters. When a strong solution of the antimicrotubule drug, MBC, was applied at anaphase A, tubulin immunocytochemistry showed that both astral and spindle microtubules were destroyed completely in less than a minute. As a result, separation of the spindle pole bodies during anaphase B almost stopped. By contrast, disrupting only the spindle microtubules with a laser microbeam increased the rate of spindle pole body separation more than fourfold. Taken together, these two experiments show that the astral forces are microtubule-dependent. When only one of the two or three bundles of spindle microtubules was broken at very early anaphase B, most such diminished spindles elongated at a normal rate, whereas others elongated at an increased rate. This result suggests that only a critical mass or number of spindle microtubules needs be present for the rate of spindle elongation to be fully governed, and that astral forces can accelerate the elongation of a weakened or diminished spindle.

scholarly journals Fission Yeast Mutants Affecting Telomere Clustering and Meiosis-Specific Spindle Pole Body Integrity

Genetics ◽  
2002 ◽  
Vol 160 (3) ◽  
pp. 861-876
Author(s):  
Ye Jin ◽  
Satoru Uzawa ◽  
W Z Cande
Keyword(s):  
Fission Yeast ◽  
Spindle Pole Body ◽  
Spindle Pole ◽  
Specific Protein ◽  
Spore Wall ◽  
Isolation And Characterization ◽  
Pole Body ◽  
Homologous Chromosome Pairing ◽  
Eukaryotic Organisms ◽  
And Function

Abstract In meiotic prophase of many eukaryotic organisms, telomeres attach to the nuclear envelope and form a polarized configuration called the bouquet. Bouquet formation is hypothesized to facilitate homologous chromosome pairing. In fission yeast, bouquet formation and telomere clustering occurs in karyogamy and persists throughout the horsetail stage. Here we report the isolation and characterization of six mutants from our screen for meiotic mutants. These mutants show defective telomere clustering as demonstrated by mislocalization of Swi6::GFP, a heterochromatin-binding protein, and Taz1p::GFP, a telomere-specific protein. These mutants define four complementation groups and are named dot1 to dot4—defective organization of telomeres. dot3 and dot4 are allelic to mat1-Mm and mei4, respectively. Immunolocalization of Sad1, a protein associated with the spindle pole body (SPB), in dot mutants showed an elevated frequency of multiple Sad1-nuclei signals relative to wild type. Many of these Sad1 foci were colocalized with Taz1::GFP. Impaired SPB structure and function were further demonstrated by failure of spore wall formation in dot1, by multiple Pcp1::GFP signals (an SPB component) in dot2, and by abnormal microtubule organizations during meiosis in dot mutants. The coincidence of impaired SPB functions with defective telomere clustering suggests a link between the SPB and the telomere cluster.

scholarly journals SFI1 promotes centriole duplication by recruiting USP9X to stabilize the microcephaly protein STIL

2019 ◽  
Vol 218 (7) ◽  
pp. 2185-2197 ◽  
Author(s):  
Andrew Kodani ◽  
Tyler Moyer ◽  
Allen Chen ◽  
Andrew Holland ◽  
Christopher A. Walsh ◽  
...  
Keyword(s):  
Mental Retardation ◽  
Mammalian Cells ◽  
Spindle Pole Body ◽  
Spindle Pole ◽  
S Phase ◽  
Loss Of Function ◽  
Centrosomal Protein ◽  
Centriole Duplication ◽  
Pole Body ◽  
Mammalian Homologue

In mammals, centrioles participate in brain development, and human mutations affecting centriole duplication cause microcephaly. Here, we identify a role for the mammalian homologue of yeast SFI1, involved in the duplication of the yeast spindle pole body, as a critical regulator of centriole duplication in mammalian cells. Mammalian SFI1 interacts with USP9X, a deubiquitylase associated with human syndromic mental retardation. SFI1 localizes USP9X to the centrosome during S phase to deubiquitylate STIL, a critical regulator of centriole duplication. USP9X-mediated deubiquitylation protects STIL from degradation. Consistent with a role for USP9X in stabilizing STIL, cells from patients with USP9X loss-of-function mutations have reduced STIL levels. Together, these results demonstrate that SFI1 is a centrosomal protein that localizes USP9X to the centrosome to stabilize STIL and promote centriole duplication. We propose that the USP9X protection of STIL to facilitate centriole duplication underlies roles of both proteins in human neurodevelopment.

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