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MBC in Press, published online ahead of print June 29, 2005
Mol. Biol. Cell 10.1091/mbc.E05-03-0213

A more recent version of this article appeared on September 1, 2005
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Submitted on March 16, 2005
Accepted on June 20, 2005

Role of the Endocytic Machinery in the Sorting of Lysosome-associated Membrane Proteins

Katy Janvier and Juan S. Bonifacino

Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892

Monitoring Editor: Suzanne Pfeffer

The limiting membrane of the lysosome contains a group of transmembrane glycoproteins named lysosome-associated membrane proteins (Lamps). These proteins are targeted to lysosomes by virtue of tyrosine-based sorting signals in their cytosolic tails. Four adaptor protein (AP) complexes, AP-1, AP-2, AP-3, and AP-4, interact with such signals and are therefore candidates for mediating sorting of the Lamps to lysosomes. However, the role of these complexes and of the coat protein, clathrin, in sorting of the Lamps in vivo has either not been addressed or remains controversial. We have used RNA interference to show that AP-2 and clathrin--and to a lesser extent the other AP complexes--are required for efficient delivery of the Lamps to lysosomes. Because AP-2 is exclusively associated with plasma membrane clathrin coats, our observations imply that a significant population of Lamps traffic via the plasma membrane en route to lysosomes.

Address correspondence to: Juan S. Bonifacino (bonifacinoj{at}mail.nih.gov)




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