The Golgi Localization of GOLPH2 (GP73/GOLM1) is Determined by the Transmembrane and Cytoplamic Sequences

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2011 Dec 6

PMID 22140547

Citations 27

Authors

Longbo Hu

Leike Li

Hongbin Xie

Yanli Gu

Tao Peng

Affiliations

Soon will be listed here.

Abstract

Golgi phosphoprotein 2 (GOLPH2) is a resident Golgi type-II membrane protein upregulated in liver disease. Given that GOLPH2 traffics through endosomes and can be secreted into the circulation, it is a promising serum marker for liver diseases. The structure of GOLPH2 and the functions of its different protein domains are not known. In the current study, we investigated the structural determinants for Golgi localization using a panel of GOLPH2 truncation mutants. The Golgi localization of GOLPH2 was not affected by the deletion of the C-terminal part of the protein. A truncated mutant containing the N-terminal portion (the cytoplasmic tail and transmembrane domain (TMD)) localized to the Golgi. Sequential deletion analysis of the N-terminal indicated that the TMD with a positively charged residue in the cytoplasmic N-terminal tail were sufficient to support Golgi localization. We also showed that both endogenous and secreted GOLPH2 exist as a disulfide-bonded dimer, and the coiled-coil domain was sufficient for dimerization. This structural knowledge is important for the understanding the pathogenic role of GOLPH2 in liver diseases, and the development of GOLPH2-based hepatocellular cancer diagnostic methods.

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References

Nufer O, Kappeler F, Guldbrandsen S, Hauri H . ER export of ERGIC-53 is controlled by cooperation of targeting determinants in all three of its domains. J Cell Sci. 2003; 116(Pt 21):4429-40. DOI: 10.1242/jcs.00759. View

Nilsson T, Pypaert M, Hoe M, Slusarewicz P, Berger E, Warren G . Overlapping distribution of two glycosyltransferases in the Golgi apparatus of HeLa cells. J Cell Biol. 1993; 120(1):5-13. PMC: 2119502. DOI: 10.1083/jcb.120.1.5. View

Gu Y, Chen W, Zhao Y, Chen L, Peng T . Quantitative analysis of elevated serum Golgi protein-73 expression in patients with liver diseases. Ann Clin Biochem. 2008; 46(Pt 1):38-43. DOI: 10.1258/acb.2008.008088. View

Wright L, Yong S, Picken M, Rockey D, Fimmel C . Decreased survival and hepato-renal pathology in mice with C-terminally truncated GP73 (GOLPH2). Int J Clin Exp Pathol. 2008; 2(1):34-47. PMC: 2491393. View

Zhou Y, Li L, Hu L, Peng T . Golgi phosphoprotein 2 (GOLPH2/GP73/GOLM1) interacts with secretory clusterin. Mol Biol Rep. 2010; 38(3):1457-62. DOI: 10.1007/s11033-010-0251-7. View

Bulbarelli A, Sprocati T, Barberi M, Pedrazzini E, Borgese N . Trafficking of tail-anchored proteins: transport from the endoplasmic reticulum to the plasma membrane and sorting between surface domains in polarised epithelial cells. J Cell Sci. 2002; 115(Pt 8):1689-702. DOI: 10.1242/jcs.115.8.1689. View

Iftikhar R, Kladney R, Havlioglu N, Schmitt-Graff A, Gusmirovic I, Solomon H . Disease- and cell-specific expression of GP73 in human liver disease. Am J Gastroenterol. 2004; 99(6):1087-95. DOI: 10.1111/j.1572-0241.2004.30572.x. View

Linstedt A, Mehta A, Suhan J, Reggio H, Hauri H . Sequence and overexpression of GPP130/GIMPc: evidence for saturable pH-sensitive targeting of a type II early Golgi membrane protein. Mol Biol Cell. 1997; 8(6):1073-87. PMC: 305715. DOI: 10.1091/mbc.8.6.1073. View

Colley K . Golgi localization of glycosyltransferases: more questions than answers. Glycobiology. 1997; 7(1):1-13. PMC: 7108620. DOI: 10.1093/glycob/7.1.1-b. View

10.

Zhang P, Shi J, Shen B, Li X, Gao Y, Zhu Z . Stejnihagin, a novel snake metalloproteinase from Trimeresurus stejnegeri venom, inhibited L-type Ca2+ channels. Toxicon. 2008; 53(2):309-15. DOI: 10.1016/j.toxicon.2008.12.006. View

11.

He Y, Huang L, Xue Y, Fei X, Teng Y, Rubin-Pitel S . Crystal structure and computational analyses provide insights into the catalytic mechanism of 2,4-diacetylphloroglucinol hydrolase PhlG from Pseudomonas fluorescens. J Biol Chem. 2009; 285(7):4603-11. PMC: 2836065. DOI: 10.1074/jbc.M109.044180. View

12.

Munro S . Localization of proteins to the Golgi apparatus. Trends Cell Biol. 1998; 8(1):11-5. PMC: 7172754. DOI: 10.1016/s0962-8924(97)01197-5. View

13.

Kladney R, Cui X, Bulla G, Brunt E, Fimmel C . Expression of GP73, a resident Golgi membrane protein, in viral and nonviral liver disease. Hepatology. 2002; 35(6):1431-40. DOI: 10.1053/jhep.2002.32525. View

14.

Kladney R, Bulla G, Guo L, Mason A, Tollefson A, SIMON D . GP73, a novel Golgi-localized protein upregulated by viral infection. Gene. 2000; 249(1-2):53-65. PMC: 7127640. DOI: 10.1016/s0378-1119(00)00136-0. View

15.

Yamaguchi N, Fukuda M . Golgi retention mechanism of beta-1,4-galactosyltransferase. Membrane-spanning domain-dependent homodimerization and association with alpha- and beta-tubulins. J Biol Chem. 1995; 270(20):12170-6. DOI: 10.1074/jbc.270.20.12170. View

16.

Munro S . Sequences within and adjacent to the transmembrane segment of alpha-2,6-sialyltransferase specify Golgi retention. EMBO J. 1991; 10(12):3577-88. PMC: 453089. View

17.

Maitra A, Thuluvath P . GP73 and liver disease: a (Golgi) complex enigma. Am J Gastroenterol. 2004; 99(6):1096-8. DOI: 10.1111/j.1572-0241.2004.40410.x. View

18.

Lundbaek J, Andersen O, Werge T, Nielsen C . Cholesterol-induced protein sorting: an analysis of energetic feasibility. Biophys J. 2003; 84(3):2080-9. PMC: 1302776. DOI: 10.1016/S0006-3495(03)75015-2. View

19.

Masibay A, Balaji P, Boeggeman E, Qasba P . Mutational analysis of the Golgi retention signal of bovine beta-1,4-galactosyltransferase. J Biol Chem. 1993; 268(13):9908-16. View

20.

Wong S, Low S, Hong W . The 17-residue transmembrane domain of beta-galactoside alpha 2,6-sialyltransferase is sufficient for Golgi retention. J Cell Biol. 1992; 117(2):245-58. PMC: 2289426. DOI: 10.1083/jcb.117.2.245. View