Abstract
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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Protein Complex alpha Subunits
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Adaptor Proteins, Vesicular Transport
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Amino Acid Sequence
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Animals
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Capsid / genetics
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Capsid / metabolism*
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Carrier Proteins*
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Cell Line
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Clathrin / metabolism
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Cloning, Molecular
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Cytosol / metabolism
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Furin
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Golgi Apparatus / metabolism*
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Membrane Proteins / metabolism*
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Mice
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Molecular Sequence Data
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Multigene Family / genetics*
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Phosphorylation
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Receptor, IGF Type 2 / metabolism
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Subtilisins / metabolism
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Vesicular Transport Proteins
Substances
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Adaptor Protein Complex alpha Subunits
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Adaptor Proteins, Vesicular Transport
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Carrier Proteins
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Clathrin
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Membrane Proteins
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Pacs1 protein, mouse
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Receptor, IGF Type 2
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Vesicular Transport Proteins
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Subtilisins
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Furin
Associated data
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GENBANK/AF076183
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GENBANK/AF076184