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Glycolipid-dependent sorting of melanosomal from lysosomal membrane proteins by lumenal determinants

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Author: Groux-Degroote, S. · Dijk, S.M. van · Wolthoorn, J. · Neumann, S. · Theos, A.C. · Mazière, A.M. de · Klumperman, J. · Meer, G. van · Sprong, H.
Type:article
Date:2008
Institution: TNO Kwaliteit van Leven
Source:Traffic, 6, 9, 951-963
Identifier: 240844
doi: doi:10.1111/j.1600-0854.2008.00740.x
Keywords: Biology · Adaptor complex · Glycosphingolipids · Lysosomal protein · Melanosomal enzyme · Melanosome assembly · Protein sorting · Secretory lysosome · chimeric protein · glucosylceramide · glycolipid · glycosphingolipid · lysosome associated membrane protein 1 · lysosome associated membrane protein 2 · membrane protein · monophenol monooxygenase · transcription factor · transcription factor ap 3 · tyrosinase related protein 1 · article · biogenesis · cell surface · cellular distribution · controlled study · Golgi complex · human · human cell · intracellular transport · lysosome · melanocyte · melanosome · priority journal · protein localization · protein targeting · protein transport · Animals · Cell Line, Tumor · Lysosome-Associated Membrane Glycoproteins · Melanocytes · Melanoma · Melanosomes · Mice · Monophenol Monooxygenase · Oxidoreductases · Protein Structure, Tertiary · Protein Transport · Transfection

Abstract

Melanosomes are lysosome-related organelles that coexist with lysosomes in mammalian pigment cells. Melanosomal and lysosomal membrane proteins share similar sorting signals in their cytoplasmic tail, raising the question how they are segregated. We show that in control melanocytes, the melanosomal enzymes tyrosinase-related protein 1 (Tyrp1) and tyrosinase follow an intracellular Golgi to melanosome pathway, whereas in the absence of glycosphingolipids, they are observed to pass over the cell surface. Unexpectedly, the lysosome-associated membrane protein 1 (LAMP-1) and 2 behaved exactly opposite: they were found to travel through the cell surface in control melanocytes but followed an intracellular pathway in the absence of glycosphingolipids. Chimeric proteins having the cytoplasmic tail of Tyrp1 or tyrosinase were transported like lysosomal proteins, whereas a LAMP-1 construct containing the lumenal domain of Tyrp1 localized to melanosomes. In conclusion, the lumenal domain contains sorting information that guides Tyrp1 and probably tyrosinase to melanosomes by an intracellular route that excludes lysosomal proteins and requires glucosylceramide. © 2008 The Authors Journal compilation © 2008 Blackwell Publishing Ltd.