Oligomer-dependent and oligomer-independent pathogenesis of muscular dystrophy-associated mutations within the penta-EF-hand domain of calpain-3
Abstract
-terminal and IS1-region processing, which were impaired by specific LGMDR1 mutations within the PEF domain. Furthermore, while WT CAPN3 predominantly localized at the sarcomeric M-bands of tibialis anterior muscles in vivo, several LGMDR1 mutants were absent from the M-bands due to decreased binding to titin, a giant cytoskeletal protein, irrespective of their oligomerization status. These findings indicate that LGMDR1 mutations within the PEF domain disrupt the physiological function of CAPN3 through both oligomer-dependent and oligomer-independent mechanisms, highlighting two distinct pathways contributing to LGMDR1 pathogenesis.
Fields of Study & Subjects
Muscle Physiology and Disorders
Calpain Protease Function and Regulation
Cardiomyopathy and Myosin Studies
Publication details
- Journal / source
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Volume
- 302
- Issue
- 4
- Pages
- 111277–111277
- Publication date
- 12 February 2026
- Language
- EN