Protein 4.1G is a membrane skeletal protein that can serve as an adapter between transmembrane proteins and the underlying membrane skeleton. The function of 4.1G remains largely unexplored. Here, using 4.1G knockout mouse embryonic fibroblasts (MEFs) as a model system, we explored the function of 4.1G in motile cells. We show that the adhesion, spreading, and migration of 4.1G(-/-) MEF cells are impaired significantly. We further show that, although the total cellular expression of β1 integrin is unchanged, the surface expression of β1 integrin and its active form are decreased significantly in 4.1G(-/-) MEF cells. Moreover, the phosphorylation of focal adhesion kinase, a downstream component of the integrin-mediated signal transduction pathway, is suppressed in 4.1G(-/-) MEF cells. Co-immunoprecipitation experiments and in vitro binding assays showed that 4.1G binds directly to β1 integrin via its membrane-binding domain. These findings identified a novel role of 4.1G in cell adhesion, spreading, and migration in MEF cells by modulating the surface expression of β1 integrin and subsequent downstream signal transduction.
Keywords: adhesion; cytoskeleton; focal adhesion kinase; membrane; migration; mouse embryonic, fibroblast; phosphorylation; protein 4.1G; spreading; β1 integrin.
© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.