GERp95, a membrane-associated protein that belongs to a family of proteinsinvolved in stem cell differentiation

A panel of mAbs was elicited against intracellular membrane fractions from rat pancreas. One of the antibodies reacted with a 95-kDa protein that loca lizes primarily to the Golgi complex or the endoplasmic reticulum (ER), dep ending on cell type. The corresponding cDNA was cloned and sequenced and fo und to encode a protein of 97.6 kDa that we call GERp95 (Golgi ER protein 9 5 kDa). The protein copurifies with intracellular membranes but does not co ntain hydrophobic regions that could function as signal peptides or transme mbrane domains. Biochemical analysis suggests that GERp95 is a cytoplasmica lly exposed peripheral membrane protein that exists in a protease-resistant complex. GERp95 belongs to a family of highly conserved proteins in metazo ans and Schizosaccharomyces pombe. It has recently been determined that pla nt and Drosophila homologues of GERp95 are important for controlling the di fferentiation of stem cells (Bohmert ct Id., 1998; Cox et al., 1998; Moussi an et al., 1998). In Caenorhabditis elegans, there are at least 20 members of this protein family. To this end, we have used RNA interference to show that the GERp95 orthologue in C. elegans is important for maturation of ger m-line stem cells in the gonad. GERp95 and related proteins are an emerging new family of proteins that have important roles in metazoan development. The present study suggests that these proteins may exert their effects on c ell differentiation from the level of intracellular membranes.