hVps41 and VAMP7 function in direct TGN to late endosome transport of lysosomal membrane proteins

Maaike S. Pols, Eline van Meel, Viola Oorschot, Corlinda ten Brink, Minoru Fukuda, M.G. Swetha, Satyajit Mayor and Judith Klumperman ()
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Maaike S. Pols: University Medical Centre Utrecht
Eline van Meel: University Medical Centre Utrecht
Viola Oorschot: University Medical Centre Utrecht
Corlinda ten Brink: University Medical Centre Utrecht
Minoru Fukuda: Glycobiology Unit, Cancer Research Center, Sanford-Burnham Medical Research Institute
M.G. Swetha: National Center for Biological Sciences
Satyajit Mayor: National Center for Biological Sciences
Judith Klumperman: University Medical Centre Utrecht

Nature Communications, 2013, vol. 4, issue 1, 1-12

Abstract: Abstract Targeted delivery of lysosome-associated membrane proteins is important for lysosome stability and function. Here we identify a pathway for transport of lysosome-associated membrane proteins directly from the trans-Golgi network to late endosomes, which exists in parallel to mannose 6-phosphate receptor and clathrin-dependent transport of lysosomal enzymes to early endosomes. By immunoelectron microscopy we localized endogenous LAMP-1 and -2 as well as LAMP-1-mGFP to non-coated, biosynthetic carriers at the trans-Golgi network and near late endosomes. These LAMP carriers were negative for mannose 6-phosphate receptor, adaptor-protein complex-1, secretory albumin and endocytic markers, but contained the homotypic fusion and protein sorting complex component hVps41 and the soluble N-ethylmaleimide-sensitive factor attachment protein receptors protein VAMP7. Knockdown of hVps41 or VAMP7 resulted in the accumulation of lysosome-associated membrane protein carriers, whereas knockdown of hVps39 or hVps18 did not, indicating that the effect of hVps41 is independent of CORVET/HOPS. Mannose 6-phosphate receptor carriers remained unaffected upon hVps41 or VAMP7 knockdown, implicating that hVps41 and VAMP7 are specifically involved in the fusion of trans-Golgi network-derived lysosome-associated membrane protein carriers with late endosomes.

Date: 2013
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DOI: 10.1038/ncomms2360

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