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Vol. 10, Issue 10, 3357-3372, October 1999

GERp95, a Membrane-associated Protein that Belongs to a Family of Proteins Involved in Stem Cell Differentiation

Darren E. Cikaluk,^* Nasser Tahbaz,^* Linda C. Hendricks, Gabriel E. DiMattia, Dave Hansen,^¶ Dave Pilgrim,^¶ and Tom C. Hobman^*

Departments of  ^*Cell Biology and  ^¶Biological Sciences, University of Alberta, Edmonton, AB, T6G 2H7, Canada;  Biological Process Sciences, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406; and  London Regional Cancer Centre, London, Ontario N6A 4L6 Canada

A panel of mAbs was elicited against intracellular membrane fractions from rat pancreas. One of the antibodies reacted with a 95-kDa protein that localizes primarily to the Golgi complex or the endoplasmic reticulum (ER), depending on cell type. The corresponding cDNA was cloned and sequenced and found to encode a protein of 97.6 kDa that we call GERp95 (Golgi ER protein 95 kDa). The protein copurifies with intracellular membranes but does not contain hydrophobic regions that could function as signal peptides or transmembrane domains. Biochemical analysis suggests that GERp95 is a cytoplasmically exposed peripheral membrane protein that exists in a protease-resistant complex. GERp95 belongs to a family of highly conserved proteins in metazoans and Schizosaccharomyces pombe. It has recently been determined that plant and Drosophila homologues of GERp95 are important for controlling the differentiation of stem cells (Bohmert et al., 1998; Cox et al., 1998; Moussian 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 germ-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 cell differentiation from the level of intracellular membranes.

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   Corresponding author. E-mail address: thobman{at}anat.med.ualberta.ca.

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Molecular Biology of the Cell
Vol. 10, 3357-3372, October 1999
Copyright © 1999 by The American Society for Cell Biology

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