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Dominant-interfering hsc70 mutants disrupt multiple stages of the clathrin-coated vesicle cycle in vivo

Academic Article
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Overview

authors

  • Newmyer, S. L.
  • Schmid, Sandra

publication date

  • February 2001

journal

  • Journal of Cell Biology  Journal

abstract

  • Within the clathrin-coated vesicle (CCV) cycle, coat assembly drives the internalization of receptors from the cell surface and disassembly allows for the processing of internalized ligands. The heat shock cognate protein, hsc70, has been implicated in regulating coat disassembly. We find that in cells overexpressing ATPase-deficient hsc70 mutants, uncoating of CCVs is inhibited in vivo, and the majority of unassembled cytosolic clathrin shifts to an assembled pool that cofractionates with AP1 and AP2. Surprisingly, this assembled pool of coat proteins accumulates in the absence of cargo receptors, suggesting that disruption of hsc70 activity may cause misassembly of empty clathrin cages. The strongest effect of overexpression of hsc70 mutants is a block in transferrin receptor (TfnR) recycling, which cannot be accounted for by the degree of inhibition of uncoating of endocytic CCVs. These results suggest that hsc70 participates in multiple transport and/or sorting events between endosomal compartments. Additionally, the mutant-expressing cells are defective at internalizing transferrin. In the most potent case, the initial rate of uptake is inhibited 10-fold, and TfnR levels double at the cell surface. Our findings demonstrate that hsc70 indeed regulates coat disassembly and also suggest that this chaperone broadly modulates clathrin dynamics throughout the CCV cycle.

subject areas

  • Adenosine Triphosphatases
  • Adenoviridae
  • Cell Fractionation
  • Clathrin
  • Clathrin-Coated Vesicles
  • Electrophoresis, Polyacrylamide Gel
  • Endocytosis
  • HSC70 Heat-Shock Proteins
  • HSP70 Heat-Shock Proteins
  • HeLa Cells
  • Humans
  • Immunoblotting
  • Kinetics
  • Microscopy, Confocal
  • Models, Biological
  • Mutation
  • Protein Structure, Tertiary
  • Protein Transport
  • Receptors, Transferrin
  • Time Factors
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Research

keywords

  • clathrin-coated vesicles
  • endocytosis
  • hsc70
  • transferrin receptor recycling
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Identity

International Standard Serial Number (ISSN)

  • 0021-9525

Digital Object Identifier (DOI)

  • 10.1083/jcb.152.3.607

PubMed ID

  • 11157986
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Additional Document Info

start page

  • 607

end page

  • 620

volume

  • 152

issue

  • 3

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