CKS1 Germ Line Exclusion Is Essential for the Transition from Meiosis to Early Embryonic Development

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985904%3A_____%2F19%3A00512107" target="_blank" >RIV/67985904:_____/19:00512107 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11310/19:10403763

Výsledek na webu

<a href="https://mcb.asm.org/content/39/13/e00590-18" target="_blank" >https://mcb.asm.org/content/39/13/e00590-18</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1128/MCB.00590-18" target="_blank" >10.1128/MCB.00590-18</a>

Jazyk výsledku

angličtina

Název v původním jazyce

CKS1 Germ Line Exclusion Is Essential for the Transition from Meiosis to Early Embryonic Development

Popis výsledku v původním jazyce

Cell division cycle (cdc) kinase subunit (CKS) proteins bind cyclin-dependent kinases (CDKs) and play important roles in cell division control and development, though their precise molecular functions are not fully understood. Mammals express two closely related paralogs called CKS1 and CKS2, but only CKS2 is expressed in the germ line, indicating that it is solely responsible for regulating CDK functions in meiosis. Using cks2(-/-) knockout mice, we show that CKS2 is a crucial regulator of maturation-promoting factor (MPF, CDK1-cyclin A/B) activity in meiosis. cks2(-/-) oocytes display reduced and delayed MPF activity during meiotic progression, leading to defects in germinal vesicle breakdown (GVBD), anaphase-promoting complex/cyclosome (APC/C) activation, and meiotic spindle assembly. cks2(-/-) germ cells express significantly reduced levels of the MPF components CDK1 and cyclins A1/B1. Additionally, injection of MPF plus CKS2, but not MPF alone, restored normal GVBD in cks2(-/- )oocytes, demonstrating that GVBD is driven by a CKS2-dependent function of MPF. Moreover, we generated cks2(cks1/cks1)( )knock-in mice and found that CKS1 can compensate for CKS2 in meiosis in vivo, but homozygous embryos arrested development at the 2- to 5-cell stage. Collectively, our results show that CKS2 is a crucial regulator of MPF functions in meiosis and that its paralog, CKS1, must be excluded from the germ line for proper embryonic development.

Název v anglickém jazyce

CKS1 Germ Line Exclusion Is Essential for the Transition from Meiosis to Early Embryonic Development

Popis výsledku anglicky

Cell division cycle (cdc) kinase subunit (CKS) proteins bind cyclin-dependent kinases (CDKs) and play important roles in cell division control and development, though their precise molecular functions are not fully understood. Mammals express two closely related paralogs called CKS1 and CKS2, but only CKS2 is expressed in the germ line, indicating that it is solely responsible for regulating CDK functions in meiosis. Using cks2(-/-) knockout mice, we show that CKS2 is a crucial regulator of maturation-promoting factor (MPF, CDK1-cyclin A/B) activity in meiosis. cks2(-/-) oocytes display reduced and delayed MPF activity during meiotic progression, leading to defects in germinal vesicle breakdown (GVBD), anaphase-promoting complex/cyclosome (APC/C) activation, and meiotic spindle assembly. cks2(-/-) germ cells express significantly reduced levels of the MPF components CDK1 and cyclins A1/B1. Additionally, injection of MPF plus CKS2, but not MPF alone, restored normal GVBD in cks2(-/- )oocytes, demonstrating that GVBD is driven by a CKS2-dependent function of MPF. Moreover, we generated cks2(cks1/cks1)( )knock-in mice and found that CKS1 can compensate for CKS2 in meiosis in vivo, but homozygous embryos arrested development at the 2- to 5-cell stage. Collectively, our results show that CKS2 is a crucial regulator of MPF functions in meiosis and that its paralog, CKS1, must be excluded from the germ line for proper embryonic development.

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

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2019

Kód důvěrnosti údajů

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

Název periodika

Molecular and Cellular Biology

ISSN

0270-7306

e-ISSN

—

Svazek periodika

39

Číslo periodika v rámci svazku

13

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

18

Strana od-do

UNSP e00590-18

Kód UT WoS článku

000471243000005

EID výsledku v databázi Scopus

2-s2.0-85068118528