Open AccessNestin contributes to skeletal muscle homeostasis and regeneration
Author(s) -
Julia Lindqvist,
Elin Torvaldson,
Josef Gullmets,
Henok Karvonen,
András Nagy,
Pekka Taimen,
John E. Eriksson
Publication year - 2017
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.202226
Subject(s) - nestin , biology , skeletal muscle , regeneration (biology) , microbiology and biotechnology , cyclin dependent kinase 5 , homeostasis , intermediate filament , medicine , endocrinology , cytoskeleton , kinase , stem cell , genetics , protein kinase a , neural stem cell , cell , cyclin dependent kinase 2
Nestin, a member of the cytoskeletal family of intermediate filaments, regulates the onset of myogenic differentiation through bidirectional signaling with the Cdk5-kinase. Here we show that these effects are also reflected at the organism level, as there is a loss of skeletal muscle mass in nestin−/− (NesKO) mice, reflected as reduced lean mass in the mice. Further examination of muscles in male mice revealed that these effects stemmed from nestin-deficient muscles being more prone to spontaneous regeneration. When the regeneration capacity of the compromised NesKO muscle was tested by muscle injury experiments, a significant healing delay was observed. NesKO satellite cells showed delayed proliferation kinetics in conjunction with an elevation in p35 levels and Cdk5 activity. These results reveal that nestin-deficiency generates a spontaneous regenerative phenotype in skeletal muscle that relates to a disturbed proliferation cycle, which is associated with uncontrolled Cdk5 activity.