Tau-tubulin kinase 2 restrains microtubule-depolymerizer KIF2A to support primary cilia growth

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F25%3A00617111" target="_blank" >RIV/86652036:_____/25:00617111 - isvavai.cz</a>

Alternative codes found

RIV/00216224:14110/25:00140714 RIV/00216208:11310/25:10515628

Result on the web

<a href="https://biosignaling.biomedcentral.com/articles/10.1186/s12964-025-02072-8" target="_blank" >https://biosignaling.biomedcentral.com/articles/10.1186/s12964-025-02072-8</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1186/s12964-025-02072-8" target="_blank" >10.1186/s12964-025-02072-8</a>

Result language

angličtina

Original language name

Tau-tubulin kinase 2 restrains microtubule-depolymerizer KIF2A to support primary cilia growth

Original language description

BackgroundPrimary cilia facilitate cellular signalling and play critical roles in development, homeostasis, and disease. Their assembly is under the control of Tau-Tubulin Kinase 2 (TTBK2), a key enzyme mutated in patients with spinocerebellar ataxia. Recent work has implicated TTBK2 in the regulation of cilia maintenance and function, but the underlying molecular mechanisms are not understood.MethodsTo dissect the role of TTBK2 during cilia growth and maintenance in human cells, we examined disease-related TTBK2 truncations. We used biochemical approaches, proteomics, genetic engineering, and advanced microscopy techniques to unveil molecular events triggered by TTBK2.ResultsWe demonstrate that truncated TTBK2 protein moieties, unable to localize to the mother centriole, create unique semi-permissive conditions for cilia assembly, under which cilia begin to form but fail to elongate. Subsequently, we link the defects in cilia growth to aberrant turnover of a microtubule-depolymerizing kinesin KIF2A, which we find restrained by TTBK2 phosphorylation.ConclusionsTogether, our data imply that the regulation of KIF2A by TTBK2 represents an important mechanism governing cilia elongation and maintenance. Further, the requirement for concentrating TTBK2 activity to the mother centriole to initiate ciliogenesis can be under specific conditions bypassed, revealing TTBK2 recruitment-independent functions of its key partner, CEP164.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10601 - Cell biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Cell communication and signaling : CCS

ISSN

1478-811X

e-ISSN

1478-811X

Volume of the periodical

23

Issue of the periodical within the volume

1

Country of publishing house

GB - UNITED KINGDOM

Number of pages

21

Pages from-to

73

UT code for WoS article

001417575100002

EID of the result in the Scopus database

2-s2.0-85218201754