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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.
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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.. b, v: @; D% F j8 K
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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.; n' M( Z4 j, } g
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In addition to μ1, PP2A had another target in the AP-1 complex. But unlike μ1, this second substrate, the ?1 subunit, was dephosphorylated on the Golgi rather than on vesicles. As ?1 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 ?1, whereas vesicle-associated PP2A favored μ1) thus restricts the activity of each subunit to the desired location.(Dephosphorylation of μ1 releases it from) |
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发表于 2009-3-6 00:50
发表于 2015-5-21 22:17
