Abstract 218: The Role of Novel Tripartite Motif Proteins in Sarcolemmal Membrane Repair
Tripartite motif (TRIM) proteins are a superfamily of coiled-coil-containing RING E3 ligases that function in many cellular processes, particularly in membrane repair pathways. Mitsugumin 53 (MG53) also known as TRIM72, is primary expressed in skeletal muscle and heart. Our experimental data confirm that during membrane damage, MG53 translocates to the injury site and acts as a molecular glue to reseal the damage area. The role of MG53 in membrane repair has been demonstrated in both in vitro studies using molecular approaches and in vivo using rodent wild type and knockout models. Thus, our data indicate that recombinant human MG53 protein can be directly applied as a therapeutic agent to increase the membrane repair capacity of many cell types, including cardiomyocytes during acute injury or in chronic disease progression. However, the precise mechanism and potential partners by which MG53 executes its membrane repair function are not completely understood. On the basis of the global TRIM family protein alignment, we hypothesize that there are other TRIM proteins that, alone or together with MG53, may facilitate repair by targeting the site of an injury. Moreover, data from our lab demonstrated that MG53 and these TRIM proteins can form homo- and hetero-oligomeric assemblies due to the presence of the coiled-coil region in these proteins and, further, that this may be necessary for the active membrane resealing process. Using E. coli protein expression methodology we can generate and isolate new TRIM recombinant proteins and test if these protein complexes are effective when applied externally to cardiac and non-cardiac cells. These novel proteins will also be tested for their pharmacokinetic properties to determine their efficacy in both acute and chronic applications. Our studies should increase our knowledge of the mechanisms controlling cardiac membrane repair and also provide novel therapeutic targets.
Author Disclosures: L.V. Gushchina: None J. Alloush: None S. Bhattacharya: None Z. Xu: None E.X. Beck: None N.L. Weisleder: None.
- © 2014 by American Heart Association, Inc.