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AP‐1 recruitment to VAMP4 is modulated by phosphorylation‐dependent binding of PACS‐1
Author(s) -
Hinners Ina,
Wendler Franz,
Fei Hao,
Thomas Laurel,
Thomas Gary,
Tooze Sharon A
Publication year - 2003
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.7400018
Subject(s) - phosphorylation , microbiology and biotechnology , chemistry , biology
The R‐SNARE VAMP4, which contains a dileucine motif, binds to the AP‐1 (adaptor protein‐1) subunit μ1a, but not μ1b, or the GGAs (Golgi‐associated gamma ear containing ARF binding proteins). Serine 20 and leucines 25,26 are essential for this binding. AP‐1 association with VAMP4 is enhanced when serine 30, in an acidic cluster, is phosphorylated by casein kinase 2. This phosphorylation‐dependent modulation of AP‐1 binding is mediated by PACS‐1 (phosphofurin acidic cluster sorting protein). Ablation of both the dileucine motif and serine 30 results in a dramatic mislocalization of VAMP4 in the regulated secretory pathway in AtT20 cells. A dominant‐negative PACS‐1, which binds acidic clusters but not AP‐1, also causes mislocalization of VAMP4. Our data support a model whereby phosphorylation‐dependent recruitment of PACS‐1 enhances AP‐1 association to cargo, and suggest that efficient retrieval depends on the formation of a complex between cargo, such as VAMP4, AP‐1 and PACS‐1.