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Tripartite motif family proteins mediate vesicular trafficking during membrane repair in striated muscle
Author(s) -
Bhattacharya Sayak,
Alloush Jenna,
Beck Eric,
Gushchina Liubov,
Weisleder Noah
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.801.2
Subject(s) - endocytosis , exocytosis , microbiology and biotechnology , internalization , biology , c2c12 , spectrin , myocyte , cytoskeleton , biochemistry , membrane , cell , myogenesis
Tripartite motif (TRIM) proteins constitute a family of proteins that all contain a canonical RING finger, B‐box and coiled‐coil domains which participate in several cellular processes. TRIM72, also known as mitsugumin 53 (MG53), is an essential component of the membrane repair machinery in striated muscles. The TRIM72/MG53 knockout mouse displays compromised muscle membrane repair and trim72 ‐/‐ mice develop skeletal myopathy and defects following cardiovascular stress. Previous studies indicate that both endocytosis and exocytosis are important in the membrane repair process, and also that TRIM72/MG53 expression can appear in vesicles that are released from myocytes. In this study we examined the role of TRIM72/MG53 in vesicular endocytosis and exocytosis in C2C12 myoblasts overexpressing TRIM72/MG53, where overexpression of TRIM72/MG53 increased both endocytosis measured by labeled dextran entry and exocytosis as assayed by transferrin internalization and recycling. Our recent findings show that TRIM72/MG53 overexpression is sufficient to activate the phosphatidylinositol‐4,5‐bisphosphate 3‐kinase (PI3K) signaling pathway. Therefore, we hypothesized that this TRIM72/MG53 mediated vesicular translocation may be regulated by a PI3K‐dependent pathway. To test this hypothesis, dextran uptake and transferrin internalization/recycling were measured in the presence of chemical and genetic inhibition of PI3K signaling. We conclude that TRIM72/MG53 is an important regulator of the PI3K signaling pathway and positively regulates translocation of vesicles to the site of membrane injury.