COMPARISON OF 3 MEMBERS OF THE CYSTEINE-RICH PROTEIN FAMILY REVEALS FUNCTIONAL CONSERVATION AND DIVERGENT PATTERNS OF GENE-EXPRESSION

Members of the cysteine-rich protein (CRP) family are evolutionarily c onserved proteins that have been implicated in the processes of cell p roliferation and differentiation. Tn particular, one CRP family member has been shown to be an essential regulator of cardiac and skeletal m uscle development, Each of the three vertebrate CRP isoforms character ized to date is composed of two copies of the zinc-binding LIM domain with associated glycine-rich repeats. In this study, we have addressed the biological significance of the CRF multigene family by comparing the subcellular distributions, biochemical properties, and expression patterns of CRP1, CRP2, and CRP3/MLP. Our data reveal that all three C RP family members, when expressed in adherent fibroblasts, associate s pecifically with the actin cytoskeleton. Moreover, all three GRP isofo rms are capable of interacting with the cytoskeletal proteins alpha-ac tinin and zyxin. Together, these observations suggest that CRP family members may exhibit overlapping cellular functions, Differences betwee n the three CRPs are evident in their protein expression patterns In c hick embryos, CRP1 expression is detected in a variety of organs enric hed in smooth muscle, CRP2 is restricted to arteries and fibroblasts., CRP3/MLP is dominant in organs enriched in striated muscle, CRP isofo rm expression is also developmentally regulated in the chick. Our find ings suggest that the three CRP family members perform similar functio ns in different muscle derivatives, The demonstration that all members of the CRP family are associated with cytoskeletal components that ha ve been implicated in the assembly and organization of filamentous act in suggests that CRPs contribute to muscle cell differentiation via ef fects on cytoarchitecture.