PDZD8 interacts with Protrudin and Rab7 at ER-late endosome membrane contact sites associated with mitochondria

Nat Commun. 2020 Jul 20;11(1):3645. doi: 10.1038/s41467-020-17451-7.

Abstract

Endosomes are compositionally dynamic organelles that regulate signaling, nutrient status and organelle quality by specifying whether material entering the cells will be shuttled back to the cell surface or degraded by the lysosome. Recently, membrane contact sites (MCSs) between the endoplasmic reticulum (ER) and endosomes have emerged as important players in endosomal protein sorting, dynamics and motility. Here, we show that PDZD8, a Synaptotagmin-like Mitochondrial lipid-binding Proteins (SMP) domain-containing ER transmembrane protein, utilizes distinct domains to interact with Rab7-GTP and the ER transmembrane protein Protrudin and together these components localize to an ER-late endosome MCS. At these ER-late endosome MCSs, mitochondria are also recruited to form a three-way contact. Thus, our data indicate that PDZD8 is a shared component of two distinct MCSs and suggest a role for SMP-mediated lipid transport in the regulation of endosome function.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Biological Transport
  • Cell Line
  • Endoplasmic Reticulum / metabolism*
  • Endosomes / metabolism*
  • Humans
  • Membrane Proteins / metabolism
  • Mitochondria / metabolism*
  • Mitochondrial Proteins / metabolism
  • Protein Transport
  • Vesicular Transport Proteins / metabolism
  • rab GTP-Binding Proteins / metabolism
  • rab7 GTP-Binding Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • Membrane Proteins
  • Mitochondrial Proteins
  • PDZD8 protein, human
  • Vesicular Transport Proteins
  • ZFYVE27 protein, human
  • rab7 GTP-Binding Proteins
  • rab7 GTP-binding proteins, human
  • rab GTP-Binding Proteins