Developmental alterations in centrosome integrity contribute to the post-mitotic state of mammalian cardiomyocytes.
Elife
; 42015 Aug 06.
Article
en En
| MEDLINE
| ID: mdl-26247711
Mammalian cardiomyocytes become post-mitotic shortly after birth. Understanding how this occurs is highly relevant to cardiac regenerative therapy. Yet, how cardiomyocytes achieve and maintain a post-mitotic state is unknown. Here, we show that cardiomyocyte centrosome integrity is lost shortly after birth. This is coupled with relocalization of various centrosome proteins to the nuclear envelope. Consequently, postnatal cardiomyocytes are unable to undergo ciliogenesis and the nuclear envelope adopts the function as cellular microtubule organizing center. Loss of centrosome integrity is associated with, and can promote, cardiomyocyte G0/G1 cell cycle arrest suggesting that centrosome disassembly is developmentally utilized to achieve the post-mitotic state in mammalian cardiomyocytes. Adult cardiomyocytes of zebrafish and newt, which are able to proliferate, maintain centrosome integrity. Collectively, our data provide a novel mechanism underlying the post-mitotic state of mammalian cardiomyocytes as well as a potential explanation for why zebrafish and newts, but not mammals, can regenerate their heart.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Diferenciación Celular
/
Centrosoma
/
Miocitos Cardíacos
/
Proliferación Celular
/
Corazón
Límite:
Animals
Idioma:
En
Revista:
Elife
Año:
2015
Tipo del documento:
Article
País de afiliación:
Alemania
Pais de publicación:
Reino Unido