Dysferlin interacts with affixin (beta-parvin) at the sarcolemma.

Abstract

The dysferlin gene is defective in Miyoshi myopathy (MM) and limb girdle muscular dystrophy type 2B (LGMD2B). Dysferlin is a sarcolemmal protein that is implicated in calcium-dependent membrane repair. Affixin (beta-parvin) is a novel, integrin-linked kinase-binding protein that is involved in the linkage between integrin and the cytoskeleton. Here we show that affixin is a dysferlin binding protein that colocalizes with dysferlin at the sarcolemma of normal human skeletal muscle. The immunoreactivity of affixin was reduced in sarcolemma of MM and LGMD2B muscles, although the total amount of the affixin protein was normal. Altered immunoreactivity of affixin was also observed in other muscle diseases including LGMD1C, where both affixin and dysferlin showed quite similar changes with a reduction of sarcolemmal staining with or without cytoplasmic accumulations. Colocalization of dysferlin and affixin was confirmed by immunofluorescence analysis using dysferlin-expressing C2 myoblasts. Wild-type and mutant dysferlin colocalized with endogenous affixin. The interaction of dysferlin and affixin was confirmed by immunoprecipitation study using normal human and mouse skeletal muscles. Using immunoprecipitation with deletion mutants of dysferlin, we have identified that C-terminal region of dysferlin is an apparent binding site for affixin. We also found N-terminal calponin homology domain of affixin as a binding site for dysferlin. Our results suggest that affixin may participate in membrane repair with dysferlin.

• Authors: Chie Matsuda, Kimihiko Kameyama, Kazuhiko Tagawa, Megumu Ogawa, Atsushi Suzuki, Satoshi Yamaji, Harumasa Okamoto, Ichizo Nishino, Yukiko K Hayashi
• Journal: Journal of neuropathology and experimental neurology (J Neuropathol Exp Neurol) Vol. 64 Issue 4 Pg. 334-40 (Apr 2005) ISSN: 0022-3069 [Print] England
• PMID: 15835269 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DYSF protein, human
• Dysferlin
• Membrane Proteins
• Muscle Proteins
• PARVB protein, human
• Parvb protein, mouse
• Actinin

Topics

• Actinin (genetics, metabolism)
• Animals
• Cell Line
• Dysferlin
• Humans
• Immunohistochemistry
• Membrane Proteins (genetics, metabolism)
• Mice
• Muscle Proteins (genetics, metabolism)
• Muscle, Skeletal (cytology, metabolism, pathology)
• Muscular Dystrophies (metabolism)
• Protein Structure, Tertiary
• Sarcolemma (chemistry, metabolism)