QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 21 February 2006
doi: 10.1242/jcs.02804

This Article Figures Only Full Text Full Text (PDF) Supplementary Material All Versions of this Article: jcs.02804v1 119/6/1080    most recent Alert me when this article is cited Alert me if a correction is posted 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Valencia, J. C. Articles by Hearing, V. J. Search for Related Content PubMed PubMed Citation Articles by Valencia, J. C. Articles by Hearing, V. J.

Sorting of Pmel17 to melanosomes through the plasma membrane by AP1 and AP2: evidence for the polarized nature of melanocytes

¹ Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
² Chemistry Department, University of Virginia, Charlottesville, VA 22904-4319, USA
³ Image Analysis Laboratory, National Cancer Institute, Frederick, MD 21702-1201, USA
⁴ Pathology Department, Health Sciences Center, University of Virginia, Charlottesville, VA 22908, USA

^* Author for correspondence (e-mail: hearingv{at}nih.gov)

Accepted 22 November 2005

Adaptor proteins (AP) play important roles in the sorting of proteins from the trans-Golgi network, but how they function in the sorting of various melanosome-specific proteins such as Pmel17, an essential structural component of melanosomes, in melanocytes is unknown. We characterized the processing and trafficking of Pmel17 via adaptor protein complexes within melanocytic cells. Proteomics analysis detected Pmel17, AP1 and AP2, but not AP3 or AP4 in early melanosomes. Real-time PCR, immunolabeling and tissue in-situ hybridization confirmed the coexpression of AP1 isoforms µ1A and µ1B (expressed only in polarized cells) in melanocytes and keratinocytes, but expression of µ1B is missing in some melanoma cell lines. Transfection with AP1 isoforms (µ1A or µ1B) showed two distinct distribution patterns that involved Pmel17, and only µ1B was able to restore the sorting of Pmel17 to the plasma membrane in cells lacking µ1B expression. Finally, we established that expression of µ1B is regulated physiologically in melanocytes by UV radiation or DKK1. These results show that Pmel17 is sorted to melanosomes by various intracellular routes, directly or indirectly through the plasma membrane, and the presence of basolateral elements in melanocytes suggests their polarized nature.

Key words: Pmel17, Plasma membrane, AP1, AP2, Melanocytes

This article has been cited by other articles:

				D. C. Harper, A. C. Theos, K. E. Herman, D. Tenza, G. Raposo, and M. S. Marks Premelanosome Amyloid-like Fibrils Are Composed of Only Golgi-processed Forms of Pmel17 That Have Been Proteolytically Processed in Endosomes J. Biol. Chem., January 25, 2008; 283(4): 2307 - 2322. [Abstract] [Full Text] [PDF]

				T. Kobayashi and V. J. Hearing Direct interaction of tyrosinase with Tyrp1 to form heterodimeric complexes in vivo J. Cell Sci., December 15, 2007; 120(24): 4261 - 4268. [Abstract] [Full Text] [PDF]

				J. C. Valencia, F. Rouzaud, S. Julien, K. G. Chen, T. Passeron, Y. Yamaguchi, M. Abu-Asab, M. Tsokos, G. E. Costin, H. Yamaguchi, et al. Sialylated Core 1 O-Glycans Influence the Sorting of Pmel17/gp100 and Determine Its Capacity to Form Fibrils J. Biol. Chem., April 13, 2007; 282(15): 11266 - 11280. [Abstract] [Full Text] [PDF]

				C. Wasmeier, M. Romao, L. Plowright, D. C. Bennett, G. Raposo, and M. C. Seabra Rab38 and Rab32 control post-Golgi trafficking of melanogenic enzymes J. Cell Biol., October 23, 2006; 175(2): 271 - 281. [Abstract] [Full Text] [PDF]

				T. Hoashi, J. Muller, W. D. Vieira, F. Rouzaud, K. Kikuchi, K. Tamaki, and V. J. Hearing The Repeat Domain of the Melanosomal Matrix Protein PMEL17/GP100 Is Required for the Formation of Organellar Fibers J. Biol. Chem., July 28, 2006; 281(30): 21198 - 21208. [Abstract] [Full Text] [PDF]