Details

Autor(en) / Beteiligte

• Crump, Colin M.
• Xiang, Yang
• Thomas, Laurel
• Gu, Feng
• Austin, Carol
• Tooze, Sharon A.
• Thomas, Gary

Titel

PACS-1 binding to adaptors is required for acidic cluster motif-mediated protein traffic

Ist Teil von

• The EMBO journal, 2001-05, Vol.20 (9), p.2191-2201

Ort / Verlag

Chichester, UK: John Wiley & Sons, Ltd

Erscheinungsjahr

2001

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• PACS‐1 is a cytosolic protein involved in controlling the correct subcellular localization of integral membrane proteins that contain acidic cluster sorting motifs, such as furin and human immunodeficiency virus type 1 (HIV‐1) Nef. We have now investigated the interaction of PACS‐1 with heterotetrameric adaptor complexes. PACS‐1 associates with both AP‐1 and AP‐3, but not AP‐2, and forms a ternary complex between furin and AP‐1. A short sequence within PACS‐1 that is essential for binding to AP‐1 has been identified. Mutation of this motif yielded a dominant‐negative PACS‐1 molecule that can still bind to acidic cluster motifs on cargo proteins but not to adaptor complexes. Expression of dominant‐negative PACS‐1 causes a mislocalization of both furin and mannose 6‐phosphate receptor from the trans‐Golgi network, but has no effect on the localization of proteins that do not contain acidic cluster sorting motifs. Furthermore, expression of dominant‐negative PACS‐1 inhibits the ability of HIV‐1 Nef to downregulate MHC‐I. These studies demonstrate the requirement for PACS‐1 interactions with adaptor proteins in multiple processes, including secretory granule biogenesis and HIV‐1 pathogenesis.