AP-1 recruitment to VAMP4 is modulated by phosphorylation-dependent binding of PACS-1.

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
EMBO Rep.
Date: Dec. 01, 2003
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