Open AccessDisruption of the Murine Calpain Small Subunit Gene, Capn4: Calpain Is Essential for Embryonic Development but Not for Cell Growth and Division
Author(s) -
J. Simon C. Arthur,
John S. Elce,
Carol Hegadorn,
Karen Williams,
Peter A. Greer
Publication year - 2000
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.20.12.4474-4481.2000
Subject(s) - calpain , biology , microbiology and biotechnology , proteases , embryonic stem cell , cell division , calpastatin , organogenesis , protein subunit , gene , cell , genetics , biochemistry , enzyme
Calpains are a family of Ca2+ -dependent intracellular cysteine proteases, including the ubiquitously expressed μ- and m-calpains. Both μ- and m-calpains are heterodimers, consisting of a distinct large 80-kDa catalytic subunit, encoded by the genesCapn1 andCapn2 , and a common small 28-kDa regulatory subunit (Capn4 ). The physiological roles and possible functional distinctions of μ- and m-calpains remain unclear, but suggested functions include participation in cell division and migration, integrin-mediated signal transduction, apoptosis, and regulation of cellular control proteins such as cyclin D1 and p53. Homozygous disruption of murineCapn4 eliminated both μ- and m-calpain activities, but this did not affect survival and proliferation of cultured embryonic stem cells or embryonic fibroblasts, or the early stages of organogenesis. However, mutant embryos died at midgestation and displayed defects in the cardiovascular system, hemorrhaging, and accumulation of erythroid progenitors.