This Article Full Text Full Text (PDF) All Versions of this Article: 19/3/749    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Munshi, U. M. Articles by Menon, K. M. J. Search for Related Content PubMed PubMed Citation Articles by Munshi, U. M. Articles by Menon, K. M. J.

Evidence that Palmitoylation of Carboxyl Terminus Cysteine Residues of the Human Luteinizing Hormone Receptor Regulates Postendocytic Processing

Departments of Biological Chemistry and Obstetrics/Gynecology, University of Michigan Medical School, Ann Arbor, Michigan 48109-0617

Address all correspondence and requests for reprints to: K. M. J. Menon, 6428 Medical Sciences Building I, 1301 Catherine Street, Ann Arbor, Michigan 48109-0617. E-mail: kmjmenon{at}umich.edu.

Palmitoylation is a well-conserved posttranslational modification among members of the G protein-coupled receptor superfamily. The present study examined the role of palmitoylation in endocytosis and postendocytic trafficking of the human LH receptor (LHR). Palmitoylation of the LHR was determined by incorporation of [³H]palmitic acid into wild-type (WT) or mutant receptor in which the potential palmitoylation sites, C643 and C644, were mutated to glycine residues. The WT receptor showed incorporation of [³H]palmitic acid into the mature 90-kDa form of the receptor whereas mutation of the two Cys residues abrogated this incorporation, indicating that Cys 643 and C644 are the sites of palmitoylation. The role of palmitoylation on endocytosis and postendocytic processing was examined by testing the ability of the WT and mutant receptor to undergo internalization, recycling, and lysosomal degradation. Compared with the WT receptor, the mutant receptor showed increased internalization and decreased recycling, suggesting that retention of palmitic acid residues at Cys 643 and 644 promotes LHR recycling. The role of palmitoylation on receptor recycling was substantiated by demonstrating that a different mutant, D578H LHR, which is deficient in palmitoylation, also recycled less efficiently. Furthermore, the data show that palmitoylation, not the rate of internalization, determines the efficiency of recycling. The present study shows that palmitoylation of cysteine residues 643 and 644 of the human LHR is a determinant of recycling.

This article has been cited by other articles:

				A. Uribe, T. Zarinan, M. A. Perez-Solis, R. Gutierrez-Sagal, E. Jardon-Valadez, A. Pineiro, J. A. Dias, and A. Ulloa-Aguirre Functional and Structural Roles of Conserved Cysteine Residues in the Carboxyl-Terminal Domain of the Follicle-Stimulating Hormone Receptor in Human Embryonic Kidney 293 Cells Biol Reprod, May 1, 2008; 78(5): 869 - 882. [Abstract] [Full Text] [PDF]

				S. P. Thankamony and W. Knudson Acylation of CD44 and Its Association with Lipid Rafts Are Required for Receptor and Hyaluronan Endocytosis J. Biol. Chem., November 10, 2006; 281(45): 34601 - 34609. [Abstract] [Full Text] [PDF]

				C. Galet and M. Ascoli A Constitutively Active Mutant of the Human Lutropin Receptor (hLHR-L457R) Escapes Lysosomal Targeting and Degradation Mol. Endocrinol., November 1, 2006; 20(11): 2931 - 2945. [Abstract] [Full Text] [PDF]