FAM110A promotes mitotic spindle formation by linking microtubules with actin cytoskeleton

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F24%3A00598889" target="_blank" >RIV/86652036:_____/24:00598889 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/68378050:_____/24:00598889

Výsledek na webu

<a href="https://www.pnas.org/doi/10.1073/pnas.2321647121" target="_blank" >https://www.pnas.org/doi/10.1073/pnas.2321647121</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1073/pnas.2321647121" target="_blank" >10.1073/pnas.2321647121</a>

Jazyk výsledku

angličtina

Název v původním jazyce

FAM110A promotes mitotic spindle formation by linking microtubules with actin cytoskeleton

Popis výsledku v původním jazyce

Precise segregation of chromosomes during mitosis requires assembly of a bipolar mitotic spindle followed by correct attachment of microtubules to the kinetochores. This highly spatiotemporally organized process is controlled by various mitotic kinases and molecular motors. We have recently shown that Casein Kinase 1 (CK1) promotes timely progression through mitosis by phosphorylating FAM110A leading to its enrichment at spindle poles. However, the mechanism by which FAM110A exerts its function in mitosis is unknown. Using structure prediction and a set of deletion mutants, we mapped here the interaction of the N- and C- terminal domains of FAM110A with actin and tubulin, respectively. Next, we found that the FAM110A-Delta 40- 61 mutant deficient in actin binding failed to rescue defects in chromosomal alignment caused by depletion of endogenous FAM110A. Depletion of FAM110A impaired assembly of F- actin in the proximity of spindle poles and was rescued by expression of the wild- type FAM110A, but not the FAM110A-Delta 40- 61 mutant. Purified FAM110A promoted binding of F- actin to microtubules as well as bundling of actin filaments in vitro. Finally, we found that the inhibition of CK1 impaired spindle actin formation and delayed progression through mitosis. We propose that CK1 and FAM110A promote timely progression through mitosis by mediating the interaction between spindle microtubules and filamentous actin to ensure proper mitotic spindle formation.

Název v anglickém jazyce

FAM110A promotes mitotic spindle formation by linking microtubules with actin cytoskeleton

Popis výsledku anglicky

Precise segregation of chromosomes during mitosis requires assembly of a bipolar mitotic spindle followed by correct attachment of microtubules to the kinetochores. This highly spatiotemporally organized process is controlled by various mitotic kinases and molecular motors. We have recently shown that Casein Kinase 1 (CK1) promotes timely progression through mitosis by phosphorylating FAM110A leading to its enrichment at spindle poles. However, the mechanism by which FAM110A exerts its function in mitosis is unknown. Using structure prediction and a set of deletion mutants, we mapped here the interaction of the N- and C- terminal domains of FAM110A with actin and tubulin, respectively. Next, we found that the FAM110A-Delta 40- 61 mutant deficient in actin binding failed to rescue defects in chromosomal alignment caused by depletion of endogenous FAM110A. Depletion of FAM110A impaired assembly of F- actin in the proximity of spindle poles and was rescued by expression of the wild- type FAM110A, but not the FAM110A-Delta 40- 61 mutant. Purified FAM110A promoted binding of F- actin to microtubules as well as bundling of actin filaments in vitro. Finally, we found that the inhibition of CK1 impaired spindle actin formation and delayed progression through mitosis. We propose that CK1 and FAM110A promote timely progression through mitosis by mediating the interaction between spindle microtubules and filamentous actin to ensure proper mitotic spindle formation.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10601 - Cell biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

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

Název periodika

Proceedings of the National Academy of Sciences of the United States of America

ISSN

0027-8424

e-ISSN

1091-6490

Svazek periodika

121

Číslo periodika v rámci svazku

29

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

11

Strana od-do

e2321647121

Kód UT WoS článku

001282943000004

EID výsledku v databázi Scopus

2-s2.0-85198975396