Elucidating the Functional Role of MLIP, a Novel Muscle A-type Lamin Interacting Protein

Abstract

A-type lamin mutations are associated with degenerative disorders causing dilated cardiomyopathy, Charcot-Marie-Tooth neuropathy and Limb-Girdle Muscular Dystrophy. Our lab has identified MLIP; a novel protein that interacts with lamin A/C. Knocked down MLIP expression in C2C12 myoblasts down regulates myogenic regulatory factors, MyoD and Myogenin, which delays myogenic differentiation. We hypothesize that MLIP is essential for myogenic differentiation. Our goal is to define the MLIP associated pathways involved in myogenic programming. Gene expression profiling of MLIP stably knocked down C2C12 cells, identified 30 genes implicated in human disease. Mutations in five of those genes (DMPK, HSPB8, LMNB2, NEFL and SGCD) cause muscular dystrophy, neuropathies, and lipodystrophies that have phenotypic overlap with laminopathies. Further studies involving the MLIP knocked down cell lines demonstrated that in the absence of puromycin, MLIP protein expression returns to normal. This in turn affects the interpretation of the gene expression data and attempted MLIP recovery experiments.