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MVB-12, a fourth subunit of metazoan ESCRT-I, functions in receptor downregulation

Academic Article
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Overview

authors

  • Audhya, A.
  • McLeod, I. X.
  • Yates III, John
  • Oegema, K.

publication date

  • September 2007

journal

  • PLoS One  Journal

abstract

  • After ligand binding and endocytosis, cell surface receptors can continue to signal from endosomal compartments until sequestered from the cytoplasm. An important mechanism for receptor downregulation in vivo is via the inward budding of receptors into intralumenal vesicles to form specialized endosomes called multivesicular bodies (MVBs) that subsequently fuse with lysosomes, degrading their cargo. This process requires four heterooligomeric protein complexes collectively termed the ESCRT machinery. In yeast, ESCRT-I is a heterotetrameric complex comprised of three conserved subunits and a fourth subunit for which identifiable metazoan homologs were lacking. Using C. elegans, we identify MVB-12, a fourth metazoan ESCRT-I subunit. Depletion of MVB-12 slows the kinetics of receptor downregulation in vivo, but to a lesser extent than inhibition of other ESCRT-I subunits. Consistent with these findings, targeting of MVB-12 to membranes requires the other ESCRT-I subunits, but MVB-12 is not required to target the remaining ESCRT-I components. Both endogenous and recombinant ESCRT-I are stable complexes with a 1:1:1:1 subunit stoichiometry. MVB-12 has two human homologs that co-localize and co-immunoprecipitate with the ESCRT-I component TSG101. Thus, MVB-12 is a conserved core component of metazoan ESCRT-I that regulates its activity during MVB biogenesis.

subject areas

  • Amino Acid Sequence
  • Animals
  • Caenorhabditis elegans
  • Down-Regulation
  • Endocytosis
  • Endosomes
  • HeLa Cells
  • Helminth Proteins
  • Humans
  • Molecular Sequence Data
  • Protein Subunits
  • Receptors, Cell Surface
  • Sequence Homology, Amino Acid
  • Vesicular Transport Proteins
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Identity

PubMed Central ID

  • PMC1978536

International Standard Serial Number (ISSN)

  • 1932-6203

Digital Object Identifier (DOI)

  • 10.1371/journal.pone.0000956

PubMed ID

  • 17895996
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Additional Document Info

start page

  • e956

volume

  • 2

issue

  • 9

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