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PMID:15623581

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Citation

Kota, J and Ljungdahl, PO (2005) Specialized membrane-localized chaperones prevent aggregation of polytopic proteins in the ER. J. Cell Biol. 168:79-88

Abstract

The integral endoplasmic reticulum (ER) membrane protein Shr3p is required for proper plasma membrane localization of amino acid permeases (AAPs) in yeast. In the absence of Shr3p AAPs are uniquely retained in the ER with each of their twelve membrane-spanning segments correctly inserted in the membrane. Here, we show that the membrane domain of Shr3p specifically prevents AAPs from aggregating, and thus, plays a critical role in assisting AAPs to fold and correctly attain tertiary structures required for ER exit. Also, we show that the integral ER proteins, Gsf2p, Pho86p, and Chs7p, function similarly to Shr3p. In cells individually lacking one of these components only their cognate substrates, hexose transporters, phosphate transporters, and chitin synthase-III, respectively, aggregate and consequently fail to exit the ER membrane. These findings indicate that polytopic membrane proteins depend on specialized membrane-localized chaperones to prevent inappropriate interactions between membrane-spanning segments as they insert and fold in the lipid bilayer of the ER membrane.

Links

PubMed PMC2171667 Online version:10.1083/jcb.200408106

Keywords

Adaptor Proteins, Vesicular Transport; Amino Acid Transport Systems/chemistry; Amino Acid Transport Systems/genetics; Amino Acid Transport Systems/metabolism; Amino Acids/metabolism; Carrier Proteins/chemistry; Carrier Proteins/metabolism; Endoplasmic Reticulum/metabolism; Intracellular Membranes/metabolism; Membrane Proteins/chemistry; Membrane Proteins/genetics; Membrane Proteins/metabolism; Molecular Chaperones/metabolism; Protein Folding; Protein Structure, Tertiary; Recombinant Fusion Proteins/genetics; Recombinant Fusion Proteins/metabolism; Saccharomyces cerevisiae/genetics; Saccharomyces cerevisiae/metabolism; Saccharomyces cerevisiae Proteins/chemistry; Saccharomyces cerevisiae Proteins/genetics; Saccharomyces cerevisiae Proteins/metabolism; Vesicular Transport Proteins

Significance

Annotations

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