Trichoplein controls microtubule anchoring at the centrosome by binding to Odf2 and ninein

Ibi, Miho; Zou, Peng; Inoko, Akihito; Shiromizu, Takashi; Matsuyama, Makoto; Hayashi, Yuko; Enomoto, Mika; Mori, Daisuke; Hirotsune, Shinji; Kiyono, Tohru; Tsukita, Sachiko; Goto, Hidemasa; Inagaki, Masaki

doi:10.1242/jcs.075705

Cited by 69 publications

(106 citation statements)

References 36 publications

(60 reference statements)

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“…Even though no membranes are thought to exist at centrosomes, both membrane and mitochondrial proteins have been found at centrosomes and basal bodies. [35][36][37][38] Notably, Mps1 binds to mortalin, which localizes to centrosomes, activates Mps1 kinase activity and is required for the ability of Mps1 to accelerate centrosome re-duplication despite also localizing to mitochondria. 39 Moreover, VDAC2 and VDAC3 were found in the non-membranous sperm outer dense fiber 19 and, thus, are not obligate membrane proteins, and VDAC2 was recently found at the base of primary cilia.…”

Section: Discussionmentioning

confidence: 99%

VDAC3 regulates centriole assembly by targeting Mps1 to centrosomes

et al. 2012

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Section: Discussionmentioning

confidence: 99%

VDAC3 regulates centriole assembly by targeting Mps1 to centrosomes

et al. 2012

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“…Furthermore, FSIP1 interacts with a number of additional proteins in the fibrous sheath, AKAP3, AKAP4, ROPN1, SPA17, and CABYR, which are all classified as CT antigens (5,11,17). ODF2 and SPAG5 are also fibrous sheath proteins that are required for centrosome and kinetochore function in tumor cells (16,18,23,24,38). Thus, the elements that regulate the microtubule-rich fibrous sheath structure could be coordinately reactivated in tumor cells, as they may confer mitotic robustness.…”

Section: Discussionmentioning

confidence: 99%

Multiple Cancer Testis Antigens Function To Support Tumor Cell Mitotic Fidelity

Cappell

Sinnott

Taus

et al. 2012

Molecular and Cellular Biology

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While the expression of genes that are normally involved in spermatogenesis is frequently detected in tumors, the extent to which these gene products are required for neoplastic behaviors is unclear. To begin to address their functional relevance to tumorigenesis, we identified a cohort of proteins which display synthetic lethality with paclitaxel in non-small-cell lung cancer and whose expression is biased toward testes and tumors. Remarkably, these testis proteins, FMR1NB, NXF2, MAGEA5, FSIP1, and STARD6, are required for accurate chromosome segregation in tumor cells. Their individual depletion enhances the generation of multipolar spindles, increases mitotic transit time, and induces micronucleation in response to an otherwise innocuous dose of paclitaxel. The underlying basis for abnormal mitosis is an alteration in microtubule function, as their depletion increases microtubule cytaster formation and disrupts microtubule stability. Given these observations, we hypothesize that reactivated testis proteins may represent unique tumor cell vulnerabilities which, if targeted, could enhance responsiveness to antimitotic therapy. Indeed, we demonstrate that combining paclitaxel with a small-molecule inhibitor of the gametogenic and tumor cell mitotic protein TACC3 leads to enhanced centrosomal abnormalities, activation of death programs, and loss of anchorage-independent growth. T umor-specific epigenetic alterations allow the activation of a panoply of otherwise silenced genetic programs that can be exploited to promote neoplastic phenotypes. In particular, genes normally involved in development and gametogenesis are frequently found to be reactivated in tumors, affording an opportunity for transformed cells to co-opt primordial cell features to confer oncogenic behaviors such as self-renewal, uncontrolled proliferation, and epithelial-to-mesenchymal transition (EMT) (1, 39). Cancer testis (CT) antigens represent one group of gametogenic proteins whose expression is otherwise biased toward the testes and reactivated in tumor cells (39). Because the testes are an immune privileged site, humoral and/or cellular responses are often elicited to CT antigens in cancer patients. Thus, much focus has surrounded exploiting these antigens as anticancer vaccine targets, while functional roles, if any, for these proteins in supporting tumor cell fitness have not been extensively evaluated. There are over 200 annotated CT antigens, and most have no known role in spermatogenesis or tumorigenesis (39). However, three recent studies implicate members of the CT antigen family in tumorigenic processes, including p53 turnover, centrosome coalescence, mitotic progression, and regulation of retinoic acid signaling (10,12,43). Furthermore, high expression of specific CT antigens in tumors has been correlated with significantly poorer outcomes, suggesting that their reactivation may enhance aggressiveness or chemoresistance (8,12,43). Therefore, uncovering roles for CT antigens and other ectopically expressed gametogenic genes could si...

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“…Taken together, these observations indicate that CAMSAP3 accumulates in the pericentrosomal area to aid release of MTs. In contrast, many centrosomal proteins, such as ninein, dynactin, CEP135, BBS4, PCM-1, Nude l and EB1 have been suggested to have a role in MT anchorage, and their depletion results in failure of centrosomal MT anchorage (Askham et al, 2002;Guo et al, 2006;Ibi et al, 2011;Louie et al, 2004;Quintyne et al, 1999). Future work will focus on the details of the mechanism of centrosomal MT anchorage.…”

Section: Camsap3 Promotes Release Of Centrosomal Mts From the Centrosomementioning

confidence: 99%

CAMSAP3 accumulates in the pericentrosomal area and accompanies microtubule release from the centrosome via katanin

Dong

Zhang

et al. 2017

Journal of Cell Science

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The epithelium has an apico-basal axis polarity that plays an important role in absorption, excretion and other physiological functions. In epithelial cells, a substantial number of non-centrosomal microtubules (MTs) are scattered in the cytoplasm with an apico-basal polarity and reorientate as epithelial cells perform different functions. Several previous studies have found that non-centrosomal MTs are nucleated at the centrosome, and then released and translocated elsewhere. However, the detailed process and molecular mechanism remain largely unknown. In this study, we found that Nezha, also called calmodulinregulated spectrin-associated protein 3 (CAMSAP3), a non-centrosomal MT minus-end protein, accumulates in the pericentrosomal area and accompanies the release of MTs from the centrosome; whereas depletion of CAMSAP3 prevented MT release and instead caused focusing of MTs at centrosomes. Further studies demonstrated that CAMSAP3 precisely coordinates with dynein and katanin to regulate the MT detachment process. In conclusion, our results indicate that CAMSAP3 is a key molecule for generation of non-centrosomal MTs.

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Trichoplein controls microtubule anchoring at the centrosome by binding to Odf2 and ninein

Cited by 69 publications

References 36 publications

VDAC3 regulates centriole assembly by targeting Mps1 to centrosomes

VDAC3 regulates centriole assembly by targeting Mps1 to centrosomes

Multiple Cancer Testis Antigens Function To Support Tumor Cell Mitotic Fidelity

CAMSAP3 accumulates in the pericentrosomal area and accompanies microtubule release from the centrosome via katanin

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