AP-1 recruitment to VAMP4 is modulated by phosphorylation-dependent binding of PACS-1.
EMBO Rep, 2003/12;4(12):1182-9.
Hinners I[1], Wendler F, Fei H, Thomas L, Thomas G, Tooze SA
Affiliations
PMID: 14608369
Impact factor: 9.071
Abstract
The R-SNARE VAMP4, which contains a dileucine motif, binds to the AP-1 (adaptor protein-1) subunit mu 1a, but not mu 1b, 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.
MeSH terms
Adaptor Protein Complex 1; Adaptor Proteins, Vesicular Transport; Adrenocorticotropic Hormone; Amino Acid Motifs; Animals; Carrier Proteins; Casein Kinase II; Cell Line; Guanosine Triphosphate; Leucine; Membrane Proteins; Mice; Mutation; Phosphorylation; Protein Binding; Protein Serine-Threonine Kinases; R-SNARE Proteins; SNARE Proteins; Serine; Transfection; Vesicular Transport Proteins; trans-Golgi Network
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