Journal of the American Society of Nephrology, Vol 3, 895-906, Copyright © 1992 by American Society of Nephrology

EDITORIALS

Glycosyl-phosphatidylinositol-anchored membrane proteins

D Brown and GL Waneck

Many proteins of eukaryotic cells are anchored to membranes by covalent linkage to glycosyl-phosphatidylinositol (GPI). These proteins lack a transmembrane domain, have no cytoplasmic tail, and are, therefore, located exclusively on the extracellular side of the plasma membrane. GPI-anchored proteins form a diverse family of molecules that includes membrane-associated enzymes, adhesion molecules, activation antigens, differentiation markers, protozoan coat components, and other miscellaneous glycoproteins. In the kidney, several GPI-anchored proteins have been identified, including uromodulin (Tamm-Horsfall glycoprotein), carbonic anhydrase type IV, alkaline phosphatase, Thy-1, BP-3, aminopeptidase P, and dipeptidylpeptidase. GPI-anchored proteins can be released from membranes with specific phospholipases and can be recovered from the detergent-insoluble pellet after Triton X-114 treatment of membranes. All GPI-anchored proteins are initially synthesized with a transmembrane anchor, but after translocation across the membrane of the endoplasmic reticulum, the ecto-domain of the protein is cleaved and covalently linked to a preformed GPI anchor by a specific transamidase enzyme. Although it remains obscure why so many proteins are endowed with a GPI anchor, the presence of a GPI anchor does confer some functional characteristics to proteins: (1) it is a strong apical targeting signal in polarized epithelial cells; (2) GPI- anchored proteins do not cluster into clathrin-coated pits but instead are concentrated into specialized lipid domains in the membrane, including so-called smooth pinocytotic vesicles, or caveoli; (3) GPI- anchored proteins can act as activation antigens in the immune system; (4) when the GPI anchor is cleaved by PI-phospholipase C or PI- phospholipase D, second messengers for signal transduction may be generated; (5) the GPI anchor can modulate antigen presentation by major histocompatibility complex molecules. Finally, at least one human disease, paroxysmal nocturnal hemoglobinuria, is a result of defective GPI anchor addition to plasma membrane proteins.

This article has been cited by other articles:

				T. Pocard, A. Le Bivic, T. Galli, and C. Zurzolo Distinct v-SNAREs regulate direct and indirect apical delivery in polarized epithelial cells J. Cell Sci., September 15, 2007; 120(18): 3309 - 3320. [Abstract] [Full Text] [PDF]

				H. Park, K. Teja, J. J. O'Shea, and R. M. Siegel The Yersinia Effector Protein YpkA Induces Apoptosis Independently of Actin Depolymerization J. Immunol., May 15, 2007; 178(10): 6426 - 6434. [Abstract] [Full Text] [PDF]

				F. R. Sheppard, M. R. Kelher, E. E. Moore, N. J. D. McLaughlin, A. Banerjee, and C. C. Silliman Structural organization of the neutrophil NADPH oxidase: phosphorylation and translocation during priming and activation J. Leukoc. Biol., November 1, 2005; 78(5): 1025 - 1042. [Abstract] [Full Text] [PDF]

				T. J. Seron, J. Hill, and P. J. Linser A GPI-linked carbonic anhydrase expressed in the larval mosquito midgut J. Exp. Biol., December 15, 2004; 207(26): 4559 - 4572. [Abstract] [Full Text] [PDF]

				T. Wimmer, G. Cohen, M. D. Saemann, and W. H. Horl Effects of Tamm-Horsfall protein on polymorphonuclear leukocyte function Nephrol. Dial. Transplant., September 1, 2004; 19(9): 2192 - 2197. [Abstract] [Full Text] [PDF]

				K. Dahan, O. Devuyst, M. Smaers, D. Vertommen, G. Loute, J.-M. Poux, B. Viron, C. Jacquot, M.-F. Gagnadoux, D. Chauveau, et al. A Cluster of Mutations in the UMOD Gene Causes Familial Juvenile Hyperuricemic Nephropathy with Abnormal Expression of Uromodulin J. Am. Soc. Nephrol., November 1, 2003; 14(11): 2883 - 2893. [Abstract] [Full Text] [PDF]

				G. J. Schwartz, A. M. Kittelberger, R. H. Watkins, and M. A. O'Reilly Carbonic anhydrase XII mRNA encodes a hydratase that is differentially expressed along the rabbit nephron Am J Physiol Renal Physiol, February 1, 2003; 284(2): F399 - F410. [Abstract] [Full Text] [PDF]

				M. A. Putnam, A. E. Moquin, M. Merrihew, C. Outcalt, E. Sorge, A. Caballero, T. A. Gondre-Lewis, and J. R. Drake Lipid Raft-Independent B Cell Receptor-Mediated Antigen Internalization and Intracellular Trafficking J. Immunol., January 15, 2003; 170(2): 905 - 912. [Abstract] [Full Text] [PDF]

				X. Zou, C. Ayling, J. Xian, T. A. Piper, P. J. Barker, and M. Bruggemann Truncation of the {micro} heavy chain alters BCR signalling and allows recruitment of CD5+ B cells Int. Immunol., December 1, 2001; 13(12): 1489 - 1499. [Abstract] [Full Text] [PDF]

				A. S. McElhinny and C. M. Warner Cross-linking of Qa-2 protein, the Ped gene product, increases the cleavage rate of C57BL/6 preimplantation mouse embryos Mol. Hum. Reprod., June 1, 2000; 6(6): 517 - 522. [Abstract] [Full Text] [PDF]

				M. G. Waugh, D. Lawson, S. K. Tan, and J. J. Hsuan Phosphatidylinositol 4-Phosphate Synthesis in Immunoisolated Caveolae-like Vesicles and Low Buoyant Density Non-caveolar Membranes J. Biol. Chem., July 3, 1998; 273(27): 17115 - 17121. [Abstract] [Full Text] [PDF]

				S. Breton, M. P. Lisanti, R. Tyszkowski, M. McLaughlin, and D. Brown Basolateral Distribution of Caveolin-1 in the Kidney: Absence from H+-ATPase-coated Endocytic Vesicles in Intercalated Cells J. Histochem. Cytochem., February 1, 1998; 46(2): 205 - 214. [Abstract] [Full Text]

				M. A. Deeg and C. B. Verchere Regulation of Glycosylphosphatidylinositol-Specific Phospholipase D Secretion from {beta}TC3 cells Endocrinology, February 1, 1997; 138(2): 819 - 826. [Abstract] [Full Text] [PDF]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673