A Golgi Lipid Signaling Pathway Controls Apical Golgi Distribution and Cell Polarity during Neurogenesis

Dev Cell. 2018 Mar 26;44(6):725-740.e4. doi: 10.1016/j.devcel.2018.02.025.

Abstract

Phosphatidylinositol (PtdIns) transfer proteins (PITPs) stimulate PtdIns-4-P synthesis and signaling in eukaryotic cells, but to what biological outcomes such signaling circuits are coupled remains unclear. Herein, we show that two highly related StART-like PITPs, PITPNA and PITPNB, act in a redundant fashion to support development of the embryonic mammalian neocortex. PITPNA/PITPNB do so by driving PtdIns-4-P-dependent recruitment of GOLPH3, and likely ceramide transfer protein (CERT), to Golgi membranes with GOLPH3 recruitment serving to promote MYO18A- and F-actin-directed loading of the Golgi network to apical processes of neural stem cells (NSCs). We propose the primary role for PITP/PtdIns-4-P/GOLPH3/CERT signaling in NSC Golgi is not in regulating bulk membrane trafficking but in optimizing apically directed membrane trafficking and/or apical membrane signaling during neurogenesis.

Keywords: CERT; GOLPH3; Golgi complex; brain development; cell polarity; neural stem cells; phosphatidylinositol transfer proteins; phosphoinositides.

Publication types

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

MeSH terms

  • Animals
  • Cell Membrane / metabolism
  • Cell Polarity*
  • Cells, Cultured
  • Embryonic Development
  • Female
  • Golgi Apparatus / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myosins / metabolism
  • Neural Stem Cells / cytology*
  • Neural Stem Cells / metabolism
  • Neurogenesis / physiology*
  • Phosphatidylinositol Phosphates / metabolism*
  • Phospholipid Transfer Proteins / physiology*
  • Phosphoproteins / metabolism
  • Signal Transduction

Substances

  • GPP34 protein, mouse
  • Myo18a protein, mouse
  • Phosphatidylinositol Phosphates
  • Phospholipid Transfer Proteins
  • Phosphoproteins
  • Pitpn protein, mouse
  • Myosins