A Rho signaling network links microtubules to PKD controlled carrier transport to focal adhesions

Elife. 2018 Jul 20:7:e35907. doi: 10.7554/eLife.35907.

Abstract

Protein kinase D (PKD) is a family of serine/threonine kinases that is required for the structural integrity and function of the Golgi complex. Despite its importance in the regulation of Golgi function, the molecular mechanisms regulating PKD activity are still incompletely understood. Using the genetically encoded PKD activity reporter G-PKDrep we now uncover a Rho signaling network comprising GEF-H1, the RhoGAP DLC3, and the Rho effector PLCε that regulate the activation of PKD at trans-Golgi membranes. We further show that this molecular network coordinates the formation of TGN-derived Rab6-positive transport carriers delivering cargo for localized exocytosis at focal adhesions.

Keywords: RhoGTPase; cell biology; golgi complex; human; microtubules; vesicle formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytoskeleton
  • Focal Adhesions / physiology*
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Microtubules / metabolism*
  • Phosphoinositide Phospholipase C / genetics
  • Phosphoinositide Phospholipase C / metabolism
  • Protein Kinase C / metabolism*
  • Protein Transport
  • Rho Guanine Nucleotide Exchange Factors / genetics
  • Rho Guanine Nucleotide Exchange Factors / metabolism
  • Signal Transduction*
  • TRPP Cation Channels / genetics
  • TRPP Cation Channels / metabolism
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / metabolism
  • rhoA GTP-Binding Protein / genetics
  • rhoA GTP-Binding Protein / metabolism
  • trans-Golgi Network / metabolism*

Substances

  • ARHGEF2 protein, human
  • Rab6 protein
  • Rho Guanine Nucleotide Exchange Factors
  • TRPP Cation Channels
  • polycystic kidney disease 1 protein
  • RHOA protein, human
  • protein kinase D
  • Protein Kinase C
  • Phosphoinositide Phospholipase C
  • phospholipase C epsilon
  • rab GTP-Binding Proteins
  • rhoA GTP-Binding Protein