Calpain 3, the "gatekeeper" of proper sarcomere assembly, turnover and maintenance.

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Serval ID
serval:BIB_C69F7A7ED6E5
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
Calpain 3, the "gatekeeper" of proper sarcomere assembly, turnover and maintenance.
Journal
Neuromuscular Disorders
Author(s)
Beckmann J.S., Spencer M.
ISSN
0960-8966
Publication state
Published
Issued date
2008
Peer-reviewed
Oui
Volume
18
Number
12
Pages
913-921
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Review
Abstract
Calpain 3 is a member of the calpain family of calcium-dependent intracellular proteases. Thirteen years ago it was discovered that mutations in calpain 3 (CAPN3) result in an autosomal recessive and progressive form of limb girdle muscular dystrophy called limb girdle muscular dystrophy type 2A. While calpain 3 mRNA is expressed at high levels in muscle and appears to have some role in developmental processes, muscles of patients and mice lacking calpain 3 still form apparently normal muscle during prenatal development; thus, a functional calpain 3 protease is not mandatory for muscle to form in vivo but it is a pre-requisite for muscle to remain healthy. Despite intensive research in this field, the physiological substrates of the calpain 3 protein (hereafter referred to as CAPN3) and its alternatively spliced isoforms remain elusive. The existence of these multiple isoforms complicates the search for the physiological functions of CAPN3 and its pathophysiological role. In this review, we summarize the genetic and biochemical evidence that point to loss of function of the full-length isoform of CAPN3, also known as p94, as the pathogenic isoform. We also argue that its natural substrates must reside in its proximity within the sarcomere where it is stored in an inactive state anchored to titin. We further propose that CAPN3 has many attributes that make it ideally suited as a sensor of sarcomeric integrity and function, involved in its repair and maintenance. Loss of these CAPN3-mediated activities can explain the "progressive" development of muscular dystrophy.
Keywords
Animals, Calpain/genetics, Calpain/metabolism, Humans, Models, Biological, Muscle Proteins/genetics, Muscle Proteins/metabolism, Muscular Dystrophies, Limb-Girdle/genetics, Muscular Dystrophies, Limb-Girdle/metabolism, Mutation, Sarcomeres/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
11/02/2009 15:24
Last modification date
20/08/2019 15:42
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