Muscular dystrophy is commonly caused by mutation in proteins that lead to sarcolemmal instability. However, work from several laboratories indicates that Miyoshi myopathy (MM) and limb girdle muscular dystrophy (LGMD) 2B, caused by defects in dysferlin expression is associated with poor healing of wounded sarcolemma. Poor healing of wounded muscles is believed to be due to poor calcium-triggered vesicle exocytosis. We have recently identified that non-dysferlin MM patient's are also poor at healing cellular wounds. Exocytosis of several different vesicles is affected by lack of dysferlin, while exocytosis of none of these vesicles appears to be deficient in non-dysferlin MM cells. Thus, it is not clear which of these (if any) vesicles are responsible for the poor healing of dysferlin deficient cells. This proposal utilizes proteomic and cell biological analysis to identify - 1) the vesicles responsible for poor healing of dysferlin-dependent and independent MM cells and 2) the molecules that regulate exocytosis of these vesicles.
. The proposed work aims to identify cellular and molecular defect responsible for a type of muscular dystrophy associated with the inability of wounded muscle cells to heal. This work would aid in prediction, diagnosis and therapy of muscular dystrophies caused by poor healing of wounded cells.
|Jaiswal, Jyoti K; Lauritzen, Stine P; Scheffer, Luana et al. (2014) S100A11 is required for efficient plasma membrane repair and survival of invasive cancer cells. Nat Commun 5:3795|
|Defour, A; Van der Meulen, J H; Bhat, R et al. (2014) Dysferlin regulates cell membrane repair by facilitating injury-triggered acid sphingomyelinase secretion. Cell Death Dis 5:e1306|
|Defour, Aurelia; Sreetama, S C; Jaiswal, Jyoti K (2014) Imaging cell membrane injury and subcellular processes involved in repair. J Vis Exp :|
|Heier, Christopher R; Damsker, Jesse M; Yu, Qing et al. (2013) VBP15, a novel anti-inflammatory and membrane-stabilizer, improves muscular dystrophy without side effects. EMBO Mol Med 5:1569-85|
|Jaiswal, Jyoti K; Simon, Sanford M (2013) Belling the cat--tagging live cells with quantum dots. Clin Chem 59:995-6|
|Jaiswal, Jyoti K; Rivera, Victor M; Simon, Sanford M (2009) Exocytosis of post-Golgi vesicles is regulated by components of the endocytic machinery. Cell 137:1308-19|