Linker region of nebulin family members plays an important role in targeting these molecules to cellular structures

The nebulin family of actin-binding proteins plays an essential role in cytoskeletal dynamics and actin filament stability. All of the family members are modular proteins with their key defining structural feature being the presence of the 35-residue nebulin modules. The family members now include nebulin, nebulette, N-RAP, LASP-1, and LIM-nebulette. Nebulin and nebulette are associated with the thin filament/Z-line junction of striated muscle. LASP-1 and LIM-nebulette are found within focal adhesions, and N-RAP is associated with muscle cellular junctions. Although much investigation has focused on the role of the interactions between nebulin modules and actin, each of these proteins contains other domains that are essential for their cellular targeting and functions. The serine-rich linker region of nebulette has previously been shown to serve just such a purpose by targeting the association of the nebulin modules to the cardiac Z-line in cultured cardiomyocytes. In this report, we analyze the targeting functions of the homologous regions of LASP-1 and LIM-nebulette in their incorporation into focal adhesions. We have found that the linker region of LASP-1 is indeed important for its cellular localization and that the shortened linker region of LIM-nebulette drives the association of nebulin modules to focal adhesions. This work was supported by grants from the National Institutes of Health-HLB and the National Council of the American Heart Association to C.L.M.