Filamin 2 (FLN2): A muscle-specific sarcoglycan interacting protein

Mutations in genes encoding for the sarcoglycans, a subset of proteins with in the dystrophin-glycoprotein complex, produce a limb-girdle muscular dyst rophy phenotype; however, the precise role of this group of proteins in the skeletal muscle is not known. To understand the role of the sarcoglycan co mplex, we looked for sarcoglycan interacting proteins with the hope of find ing novel members of the dystrophin-glycoprotein complex. Using the yeast t wo-hybrid method, we have identified a skeletal muscle-specific form of fil amin, which we term filamin 2 (FLN2), as a gamma- and delta-sarcoglycan int eracting protein. In addition, we demonstrate that FLN2 protein localizatio n in limb-girdle muscular dystrophy and Duchenne muscular dystrophy patient s and mice is altered when compared with unaffected individuals. Previous s tudies of filamin family members have determined that these proteins are in volved in actin reorganization and signal transduction cascades associated with cell migration, adhesion, differentiation, force transduction, and sur vival. Specifically, filamin proteins have been found essential in maintain ing membrane integrity during force application. The finding that FLN2 inte racts with the sarcoglycans introduces new implications for the pathogenesi s of muscular dystrophy.