Higher order structure of the PCM adjacent to the centriole

Ou, Young Y.; Zhang, Meifeng; Chi, Simon; Matyas, John R.; Rattner, J. B.

doi:10.1002/cm.10115

Cited by 22 publications

(27 citation statements)

References 33 publications

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“…However, it was previously reported that the PCM is not homogeneous and that some centrosomal proteins are closely associated with the centriole to form a distinct PCM compartment called the ''PCM tube'' while others are more peripheral (Bornens 2002;Ou et al 2003). Taken together, we have a similar conclusion to that of Varmark et al (2007)-that Asl is localized at the periphery of the centriole-but we showed that it is not a structural component of the centriole.…”

Section: Resultssupporting

confidence: 77%

Drosophilaasterlessand Vertebrate Cep152 Are Orthologs Essential for Centriole Duplication

et al. 2008

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The centriole is the core structure of centrosome and cilium. Failure to restrict centriole duplication to once per cell cycle has serious consequences and is commonly observed in cancer. Despite its medical importance, the mechanism of centriole formation is poorly understood. Asl was previously reported to be a centrosomal protein essential for centrosome function. Here we identify mecD, a severe loss-of-function allele of the asl gene, and demonstrate that it is required for centriole and cilia formation. Similarly, Cep152, the Asl ortholog in vertebrates, is essential for cilia formation and its function can be partially rescued by the Drosophila Asl. The study of Asl localization suggests that it is closely associated with the centriole wall, but is not part of the centriole structure. By analyzing the biogenesis of centrosomes in cells depleted of Asl, we found that, while pericentriolar material (PCM) function is mildly affected, Asl is essential for daughter centriole formation. The clear absence of several centriolar markers in mecD mutants suggests that Asl is critical early in centriole duplication.

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Section: Resultssupporting

confidence: 77%

Drosophilaasterlessand Vertebrate Cep152 Are Orthologs Essential for Centriole Duplication

et al. 2008

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“…Instead, one view of BBS6 appeared as distinctive 'O-shaped' structures surrounding γ-tubulin (Fig. 4A), suggesting that BBS6 is part of the PCM tube structure characterized by Ou et al (Ou et al, 2003). To test this possibility, we co-stained interphase or mitotic cells with our anti-BBS6 antibody and serum (M4491) that specifically recognizes a subset of PCM proteins forming a tube-like structure around centrioles (Mack et al, 1998).…”

Section: Bbs6 Is Not Associated With Cct and Is Enriched In Centrosommentioning

confidence: 92%

MKKS/BBS6, a divergent chaperonin-like protein linked to the obesity disorder Bardet-Biedl syndrome, is a novel centrosomal component required for cytokinesis

Kim

Badano

et al. 2005

Journal of Cell Science

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Chaperonins are multisubunit, cylinder-shaped molecular chaperones involved in folding newly synthesized polypeptides. Here we show that MKKS/BBS6, one of several proteins associated with Bardet-Biedl syndrome (BBS), is a Group II chaperonin-like protein that has evolved recently in animals from a subunit of the eukaryotic chaperonin CCT/TRiC, and diverged rapidly to acquire distinct functions. Unlike other chaperonins, cytosolic BBS6 does not oligomerize, and the majority of BBS6 resides within the pericentriolar material (PCM), a proteinaceous tube surrounding centrioles. During interphase, BBS6 is confined to the lateral surfaces of the PCM but during mitosis it relocalizes throughout the PCM and is found at the intercellular bridge. Its predicted substrate-binding apical domain is sufficient for centrosomal association, and several patient-derived mutations in this domain cause mislocalization of BBS6. Consistent with an important centrosomal function, silencing of the BBS6 transcript by RNA interference in different cell types leads to multinucleate and multicentrosomal cells with cytokinesis defects. The restricted tissue distribution of BBS6 further suggests that it may play important roles in ciliated epithelial tissues, which is consistent with the probable functions of BBS proteins in basal bodies (modified centrioles) and cilia. Our findings provide the first insight into the nature and cellular function of BBS6, and shed light on the potential causes of several ailments, including obesity, retinal degeneration, kidney dysfunction and congenital heart disease.

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“…Through the cell cycle, the PCM varies in volume and the MT-nucleating activity, which are smallest in G1-phase and biggest during mitosis. In addition, proteins have a precise and cell cycle-specific placement within the PCM that has been observed as a tubular structure located along the surface of the centriole and around its proximal end but not around its distal end (Ou and Rattner, 2000;Ou et al, 2003). The outer surface of the PCM is dynamic and PCM proteins found in the cytoplasm transit to the PCM either by diffusion or via MTs.…”

mentioning

confidence: 99%

CDK5RAP2 Is a Pericentriolar Protein That Functions in Centrosomal Attachment of the γ-Tubulin Ring Complex

Fong

Choi

Rattner

et al. 2008

MBoC

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243

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Microtubule nucleation and organization by the centrosome require ␥-tubulin, a protein that exists in a macromolecular complex called the ␥-tubulin ring complex (␥TuRC). We report characterization of CDK5RAP2, a novel centrosomal protein whose mutations have been linked to autosomal recessive primary microcephaly. In somatic cells, CDK5RAP2 localizes throughout the pericentriolar material in all stages of the cell cycle. When overexpressed, CDK5RAP2 assembled a subset of centrosomal proteins including ␥-tubulin onto the centrosomes or under the microtubule-disrupting conditions into microtubule-nucleating clusters in the cytoplasm. CDK5RAP2 associates with the ␥TuRC via a short conserved sequence present in several related proteins found in a range of organisms from fungi to mammals. The binding of CDK5RAP2 is required for ␥TuRC attachment to the centrosome but not for ␥TuRC assembly. Perturbing CDK5RAP2 function delocalized ␥-tubulin from the centrosomes and inhibited centrosomal microtubule nucleation, thus leading to disorganization of interphase microtubule arrays and formation of anastral mitotic spindles. Together, CDK5RAP2 is a pericentriolar structural component that functions in ␥TuRC attachment and therefore in the microtubule organizing function of the centrosome. Our findings suggest that centrosome malfunction due to the CDK5RAP2 mutations may underlie autosomal recessive primary microcephaly. INTRODUCTIONIn animal cells, the centrosome is the primary microtubule (MT) organizing center (MTOC), which plays a key role in the control of the temporal and spatial distribution of MT networks (Ou and Rattner, 2004;Doxsey et al., 2005;Luders and Stearns, 2007). Typically, centrosomes are positioned at the focus of a radial array of MTs during interphase and are incorporated into spindle poles during mitosis. Interphase centrosomes are composed of a pair of centrioles embedded in a cloud of electron-dense pericentriolar material (PCM). The centriole has a well-defined structure with MT triplets arranged into a cylinder, whereas the organization of the PCM is less apparent. Early studies have shown the existence of a salt (2 M KI)-insoluble scaffold/matrix underlying the PCM (Moritz et al., 1998;Schnackenberg et al., 1998). This matrix, formed with a high content of large coiled-coil proteins, provides binding sites for the tubulin family member ␥-tubulin and other proteins associated with centrosomal functions, such as MT nucleation. Through the cell cycle, the PCM varies in volume and the MT-nucleating activity, which are smallest in G1-phase and biggest during mitosis. In addition, proteins have a precise and cell cycle-specific placement within the PCM that has been observed as a tubular structure located along the surface of the centriole and around its proximal end but not around its distal end (Ou and Rattner, 2000;Ou et al., 2003). The outer surface of the PCM is dynamic and PCM proteins found in the cytoplasm transit to the PCM either by diffusion or via MTs.Distributed throughout the PCM, ␥-tubulin ...

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Higher order structure of the PCM adjacent to the centriole

Cited by 22 publications

References 33 publications

Drosophilaasterlessand Vertebrate Cep152 Are Orthologs Essential for Centriole Duplication

Drosophilaasterlessand Vertebrate Cep152 Are Orthologs Essential for Centriole Duplication

MKKS/BBS6, a divergent chaperonin-like protein linked to the obesity disorder Bardet-Biedl syndrome, is a novel centrosomal component required for cytokinesis

CDK5RAP2 Is a Pericentriolar Protein That Functions in Centrosomal Attachment of the γ-Tubulin Ring Complex

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