Article
- The EMBO Journal (2001) 20, 2191 - 2201
- doi:10.1093/emboj/20.9.2191
PACS-1 binding to adaptors is required for acidic cluster motif-mediated protein traffic
Colin M. Crump1,4, Yang Xiang2,4, Laurel Thomas1, Feng Gu1, Carol Austin3, Sharon A. Tooze3 and Gary Thomas1
- Vollum Institute, L-474, Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR 97201-3098, USA
- HHMI, Beckman Center B161, Stanford University, Palo Alto, CA 94304, USA
- Imperial Cancer Research Fund, PO Box 123, Lincoln Inn Fields, London WC2A 3PX, UK
- C.M.Crump and Y.Xiang contributed equally to this work
Correspondence to:
Gary Thomas, E-mail: thomasg@ohsu.edu
Received 14 November 2000; Accepted 13 March 2001; Revised 26 February 2001
Abstract
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.
Keywords:
- adaptors,
- furin,
- Nef,
- PACS-1,
- secretory granule



