Protein products of human Gas2-related genes on chromosomes 17 and 22 (hGAR17 and hGAR22) associate with both microfilaments and microtubules

Abstract

The human Gas2-related gene on chromosome 22 (hGAR22)encodes two alternatively spliced mRNA species. The longer mRNA encodes a protein with a deduced molecular mass of 36.3 kDa (GAR22α), whereas the shorter mRNA encodes a larger protein with a deduced molecular mass of 72.6 kDa (GAR22β). We show that both hGAR22 proteins contain a calponin homology actin-binding domain and a Gas2-related microtubule-binding domain. Using rapid amplification of cDNA ends, we have cloned the mouse orthologue of hGAR22, mGAR22, and found its protein products to be extremely well conserved. We also report the cDNA cloning of a human Gas2-related gene on chromosome 17(hGAR17). hGAR17 also encodes two protein isoforms. The overall cytoskeletal binding properties of the hGAR17 and hGAR22 proteins are remarkably similar. hGAR17 mRNA expression is limited to skeletal muscle. Although hGAR22 and mGAR22 mRNAs are expressed nearly ubiquitously, mGAR22 protein can only be detected in testis and brain. Furthermore, only the βisoform is present in these tissues. GAR22β expression is induced in a variety of cultured cells by growth arrest. The absolute amounts of GAR22β protein expressed are low. The β isoforms of hGAR17 and hGAR22 appear to be able to crosslink microtubules and microfilaments in transfected cells. This finding suggests that the physiological functions of these proteins may involve integration of these two components of the cytoskeleton.