Utrophin is a calpain substrate in muscle cells.

Abstract:

:Calpains are Ca2+ -dependent cytosolic cysteine proteases that participate in the pathology of Duchenne muscular dystrophy (DMD). Utrophin is a functional homolog of dystrophin that partially compensates for dystrophin deficiency in myofibers of mdx mice. In this study, we investigated the susceptibility of utrophin to cleavage by calpain in vitro and in muscle cells. We found that utrophin is a direct in vitro substrate of purified calpain I and II. Cleavage of utrophin by calpain I or II generates specific degradation products that are also found in cultured control and DMD myotubes under conditions with elevated intracellular Ca2+ levels. In addition, we showed that activation of cellular calpains by Ca2+ ionophore treatment reduces utrophin protein levels in muscle cells and that calpain inhibition prevents this Ca2+ -induced reduction in utrophin levels. These observations suggest that, beside its known effect on general muscle protein degradation, calpain contributes to DMD pathology by specifically degrading the compensatory protein utrophin.

journal_name

Muscle Nerve

journal_title

Muscle & nerve

authors

Courdier-Fruh I,Briguet A

doi

10.1002/mus.20549

subject

Has Abstract

pub_date

2006-06-01 00:00:00

pages

753-9

issue

6

eissn

0148-639X

issn

1097-4598

journal_volume

33

pub_type

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