Regulation of microtubule stability by centrosomal proteins

Kumari, Anuradha; Panda, Dulal

doi:10.1002/iub.1865

Cited by 12 publications

(5 citation statements)

References 78 publications

(137 reference statements)

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“…Several centrosomal proteins have been found to have important roles in the cell cycle progression [1][2][3][4][5][6][7]. STARD9, (steroidogenic acute regulatory protein-related lipid transfer (START) domain containing 9), is one of the newly identified centrosomal proteins that binds to mitotic microtubules and thought to have a role in spindle pole assembly [8,9].…”

Section: Introductionmentioning

confidence: 99%

A centrosomal protein STARD9 promotes microtubule stability and regulates spindle microtubule dynamics

Srivastava

Panda

2018

Cell Cycle

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Centrosomal proteins play important roles in the spindle assembly and the segregation of chromosomes in the eukaryotic cells. STARD9, a recently identified centrosomal protein, was reported to influence the spindle pole assembly. However, the role of STARD9 in maintaining the stability and organization of microtubules are not known. Here, we show that STARD9 regulates the assembly and dynamics of both interphase and mitotic microtubules. The knockdown of STARD9 in HeLa or HCT116 cells with siRNA or shRNA induced a strong depolymerization of the interphase microtubules. The over-expression of the motor domain of STARD9 stabilizes microtubules against cold and nocodazole suggesting that STARD9 stabilizes microtubules in HeLa cells. Using fluorescent recovery after photobleaching, we showed that the knockdown of STARD9 strongly reduced microtubule dynamics in the live spindles of HeLa cells. The reassembly of microtubules in the STARD9-depleted cells was strongly reduced as compared to the microtubules in the control cells implying the role of STARD9 in the nucleation of microtubules. Further, the depletion of STARD9 inhibited chromosome separation and the STARD9-depleted HeLa cells were blocked at mitosis. Interestingly, the frequency of multipolar spindle formation increased significantly in the STARD9-depleted HeLa cells in the presence of vinblastine and the STARD9-depleted cells showed much higher sensitivity towards vinblastine than the control cells indicating a new approach for cancer chemotherapy. The evidence suggests that STARD9 regulates the assembly and stability of both interphase and spindle microtubules and thereby, play important roles in the cell cycle progression.

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Section: Introductionmentioning

confidence: 99%

A centrosomal protein STARD9 promotes microtubule stability and regulates spindle microtubule dynamics

Srivastava

Panda

2018

Cell Cycle

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“…These results suggest that the reduction of other PCM proteins (Ninein, PCM1, and EB1) in SART1-depleted extracts is not caused by the partial reduction of Cep192 but due to a direct, specific effect of the SART1 absence. PCMs proteins recruited by SART1 could promote MT dynamics and, as a result, contribute to chromosome alignment (Foley and Kapoor, 2013; Kumari and Panda, 2018).…”

Section: Discussionmentioning

confidence: 99%

SART1 localizes to spindle poles forming a SART1 cap and promotes spindle pole assembly

Yokoyama,

Moreno-Andrés,

Takizawa

et al. 2023

Preprint

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The nuclear protein SART1 has been associated with pre-mRNA splicing but SART1 RNAi knockdown results also in defects in mitotic progression, centrosome biogenesis and chromosome cohesion. The mitotic roles of SART1 have not been characterized in detail and it remains unclear whether SART1 functions in mitosis directly or indirectly via pre-mRNA splicing. Here, we identify SART1 as a direct, mitosis-specific microtubule-associated protein. SART1 downregulation in human cells leads to spindle assembly defects with reduced microtubule dynamics, lack of end-on attachment, and checkpoint activation, while microtubule dynamics remain unaffected in interphase. SART1 uniquely localizes to the distal surface of mitotic centrosomes along the spindle axis, forming a previously not described structure we refer to as SART1 cap. Immunoprecipitation of SART1 consistently identifies centrosomal proteins as interaction partners. Immunostaining of these shows that SART1 downregulation does not affect centriole duplication and centrosome-accumulation of γ-tubulin but reduces the accumulation of selective pericentriolar material (PCM) proteins like Ninein. Depletion of SART1 from frog egg extracts disrupts spindle pole assembly around sperm nuclei and DNA-coated beads. Spindles formed around DNA-coated beads do not contain centrosomes but still recruits PCM proteins for spindle pole assembly. We finally show that the N-terminus of SART1 is its microtubule-binding region and essential for spindle assembly. Our data unravel a unique localization of SART1 and a novel function to recruit selective PCM proteins for spindle pole assembly in centrosomal and acentrosomal spindle assembly.

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“…Regulation of microtubule dynamics in cells is a complex process involving the coordinated activity of several proteins, including MAPs, centrosomal proteins, motor proteins, and several protein kinases that control the activation and recruitment of the nucleating factors (Bodakuntla et al, 2019; Kumari and Panda, 2018; Prassanawar and Panda, 2019; Tovey and Conduit, 2018). We propose CEP41 as another member of this regulatory network with newly identified microtubule-stabilizing activity.…”

Section: Discussionmentioning

confidence: 99%

CEP41, a ciliopathy-linked centrosomal protein, regulates microtubule assembly and cell proliferation

Prassanawar,

Sarkar,

Panda

2023

Preprint

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Centrosomal proteins play pivotal roles in orchestrating microtubule dynamics, and their dysregulation leads to various disorders, including cancer and ciliopathies. Understanding the multifaceted roles of centrosomal proteins is vital to comprehend their involvement in disease development. Here, we report novel cellular functions of CEP41, a centrosomal and ciliary protein implicated in Joubert syndrome, a neurodevelopmental ciliopathy. We show that CEP41 is an essential microtubule-associated protein with microtubule-stabilizing activity.In vitro, purified CEP41 binds to preformed microtubules, promotes microtubule nucleation, and suppresses microtubule disassembly. When overexpressed in cultured cells, CEP41 localizes to microtubules and promotes formation of stable microtubule bundles. Conversely, shRNA-mediated knockdown of CEP41 causes disassembly of the interphase microtubule network, emphasizing its role in microtubule organization. Using GFP-tagged deletion constructs, we demonstrate that CEP41’s association with microtubules relies on its conserved rhodanese homology domain and the N- terminal region. Furthermore, CEP41 depletion inhibits cell proliferation and induces G1 arrest, suggesting its potential role in cell cycle regulation. These insights into the cellular functions of CEP41 hold promise for unraveling the impact of its mutations in ciliopathies.SummaryA novel role of CEP41 as a microtubule-associated protein that promotes microtubule assembly and regulates cell cycle progression could offer insights into the development of ciliopathies.

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Regulation of microtubule stability by centrosomal proteins

Cited by 12 publications

References 78 publications

A centrosomal protein STARD9 promotes microtubule stability and regulates spindle microtubule dynamics

A centrosomal protein STARD9 promotes microtubule stability and regulates spindle microtubule dynamics

SART1 localizes to spindle poles forming a SART1 cap and promotes spindle pole assembly

CEP41, a ciliopathy-linked centrosomal protein, regulates microtubule assembly and cell proliferation

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