PACS-1 defines a novel gene family of cytosolic sorting proteins required for trans-Golgi network localization.
We report the role of one member of a novel gene family, PACS-1, in the localization of trans-Golgi network (TGN) membrane proteins. PACS-1 directs the TGN localization of furin by binding to the protease's phosphorylated cytosolic domain. Antisense studies show TGN localization of furin and mannose-6-phosphate receptor, but not TGN46, is strictly dependent on PACS-1. Analyses in vitro and in vivo show PACS-1 has properties of a coat protein and connects furin to components of the clathrin-sorting machinery. Cell-free assays indicate TGN localization of furin is directed by a PACS-1-mediated retrieval step. Together, these findings explain a mechanism by which membrane proteins in mammalian cells are localized to the TGN.
Vollum Institute, The Oregon Health Sciences University, Portland 97201, USA.
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Wan
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Molloy
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Thomas
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Liu
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Xiang
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Rybak
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Thomas
D033965:Adaptor Protein Complex alpha Subunits; D033942:Adaptor Proteins, Vesicular Transport; D000595:Amino Acid Sequence; D000818:Animals; D002213:Capsid / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins; D002460:Cell Line; D002966:Clathrin / Q000378:metabolism; D003001:Cloning, Molecular; D003600:Cytosol / Q000378:metabolism; D045683:Furin; D006056:Golgi Apparatus / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics*; D010766:Phosphorylation; D017527:Receptor, IGF Type 2 / Q000378:metabolism; D013381:Subtilisins / Q000378:metabolism; D033921:Vesicular Transport Proteins
D033965:Adaptor Protein Complex alpha Subunits; D033942:Adaptor Proteins, Vesicular Transport; D002352:Carrier Proteins; D002966:Clathrin; D008565:Membrane Proteins; C491913:Pacs1 protein, mouse; D017527:Receptor, IGF Type 2; D033921:Vesicular Transport Proteins; D013381:Subtilisins; D045683:Furin