Differential physiological roles for BIN1 isoforms in skeletal muscle development, function and regeneration.
Dis Model Mech
; 13(11)2020 11 24.
Article
em En
| MEDLINE
| ID: mdl-32994313
ABSTRACT
Skeletal muscle development and regeneration are tightly regulated processes. How the intracellular organization of muscle fibers is achieved during these steps is unclear. Here, we focus on the cellular and physiological roles of amphiphysin 2 (BIN1), a membrane remodeling protein mutated in both congenital and adult centronuclear myopathies (CNM), that is ubiquitously expressed and has skeletal muscle-specific isoforms. We created and characterized constitutive muscle-specific and inducible Bin1 homozygous and heterozygous knockout mice targeting either ubiquitous or muscle-specific isoforms. Constitutive Bin1-deficient mice died at birth from lack of feeding due to a skeletal muscle defect. T-tubules and other organelles were misplaced and altered, supporting a general early role for BIN1 in intracellular organization, in addition to membrane remodeling. Although restricted deletion of Bin1 in unchallenged adult muscles had no impact, the forced switch from the muscle-specific isoforms to the ubiquitous isoforms through deletion of the in-frame muscle-specific exon delayed muscle regeneration. Thus, ubiquitous BIN1 function is necessary for muscle development and function, whereas its muscle-specific isoforms fine tune muscle regeneration in adulthood, supporting that BIN1 CNM with congenital onset are due to developmental defects, whereas later onset may be due to regeneration defects.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Regeneração
/
Músculo Esquelético
/
Proteínas Supressoras de Tumor
/
Desenvolvimento Muscular
/
Proteínas Adaptadoras de Transdução de Sinal
/
Proteínas do Tecido Nervoso
Limite:
Animals
Idioma:
En
Revista:
Dis Model Mech
Assunto da revista:
MEDICINA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
França