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Dephosphorylation of µ1 releases it from cargo and lets AP-1 off vesicles.

Clathrin-coated vesicles (CCVs) that traffic between the trans-Golgi network and endosomes are nucleated by the adaptor protein complex-1 (AP-1). AP-1 sorts and packages cargo into CCVs and then falls off the vesicles before they arrive at their destination. On page 699, Ghosh and Kornfeld demonstrate that two of the four AP-1 subunits are opposingly phosphorylated and dephosphorylated. The regulatory cycles control vesicle trafficking by turning on cargo recruitment and clathrin coating at the appropriate time.

Cargo recruitment is mediated by the µ1 subunit of AP-1. The authors demonstrate that µ1 is phosphorylated on the membrane and dephosphorylated in the cytosol. Phosphorylation induced a conformational change in µ1 that increased its affinity for cargo ligands. Addition of a phosphate group also alters the conformation of the µ2 subunit of AP-2, which regulates vesicle formation at the plasma membrane.

Dephosphorylation by protein phosphatase 2A (PP2A) reversed the shape change and allowed µ1 to release the cargo. As a result, AP-1 disembarks from the vesicle and returns to the cytosol. PP2A is recruited to vesicles by Hsc-70, which is also required for uncoating. In combination, PP2A and Hsc-70 released both AP-1 and AP-2 from vesicles in vitro, suggesting that dephosphorylation is a common uncoating mechanism.

In addition to µ1, PP2A had another target in the AP-1 complex. But unlike µ1, this second substrate, the ß1 subunit, was dephosphorylated on the Golgi rather than on vesicles. As ß1 phosphorylation impairs its ability to interact with clathrin, PP2A activity is necessary for CCV formation. The opposing preference for substrates based on location (Golgi-associated PP2A preferred ß1, whereas vesicle-associated PP2A favored µ1) thus restricts the activity of each subunit to the desired location.

Nicole LeBrasseur

lebrasn{at}rockefeller.edu

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This Article PDF (Full Text) Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by LeBrasseur, N. Search for Related Content PubMed Articles by LeBrasseur, N. Related Collections Related Article Social Bookmarking                      What's this?