Dual function of MG53 in membrane repair and insulin signaling

Abstract

MG53 is a member of the TRIM-family protein that acts as a key component of the cell membrane repair machinery. MG53 is also an E3-ligase that ubiquinates insulin receptor substrate-1 and controls insulin signaling in skeletal muscle cells. Since its discovery in 2009, research efforts have been devoted to translate this basic discovery into clinical applications in human degenerative and metabolic diseases. This review article highlights the dual function of MG53 in cell membrane repair and insulin signaling, the mechanism that underlies the control of MG53 function, and the therapeutic value of targeting MG53 function in regenerative medicine. [BMB Reports 2016; 49(8): 414-423].

Fig. 1.. MG53 function in cell membrane repair and insulin signaling. (A) MG53 contains 477 amino acids with RING (Really Interesting New Gene), B-box, and Coil-coil domain at the amino terminus, plus a SPRY domain at the carboxyl terminus. (B) MG53 participates in the nucleation of transport vesicles to sites of membrane injury. It binds to phosphatidylserine (PS) and undergoes oligomerization when the cell changes from reduced to oxidized environment at the injury site. Entry of extracellular Ca²⁺ enables fusion of vesicles for formation of a repair patch. (C) MG53 contains an E3 Ligase activity that facilitates the ubiquitination of IRS-1. The proteasome-mediated degradation of IRS-1 contributes to the regulation of insulin signaling in muscle cells.