PDZD8 mediates a Rab7-dependent interaction of the ER with late endosomes and lysosomes

Proc Natl Acad Sci U S A. 2019 Nov 5;116(45):22619-22623. doi: 10.1073/pnas.1913509116. Epub 2019 Oct 21.

Abstract

Contacts between the endoplasmic reticulum (ER) and other membranes are hot spots for protein-mediated lipid transport between the 2 adjacent bilayers. Compiling a molecular inventory of lipid transport proteins present at these sites is a premise to the elucidation of their function. Here we show that PDZD8, an intrinsic membrane protein of the ER with a lipid transport module of the SMP domain family, concentrates at contacts between the ER and late endosomes/lysosomes, where it interacts with GTP-Rab7. These findings suggest that PDZD8 may cooperate with other proteins that function at the ER-endo/lysosome interface in coordinating endocytic flow with lipid transport between endocytic membranes and the ER.

Keywords: SMP domain; lipid-transfer protein; membrane contact sites.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Cell Membrane / genetics
  • Cell Membrane / metabolism
  • Endoplasmic Reticulum / genetics
  • Endoplasmic Reticulum / metabolism*
  • Endosomes / genetics
  • Endosomes / metabolism*
  • Humans
  • Lysosomes / genetics
  • Lysosomes / metabolism*
  • Protein Binding
  • Protein Domains
  • Protein Transport
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / metabolism*
  • rab7 GTP-Binding Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • PDZD8 protein, human
  • rab7 GTP-Binding Proteins
  • rab7 GTP-binding proteins, human
  • rab GTP-Binding Proteins