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A Golgi lipid signaling pathway that controls neural stem cell polarity in the developing neocortex
Author(s) -
Bankaitis Vytas,
Xie Zhigang
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.103.2
Subject(s) - golgi apparatus , microbiology and biotechnology , biology , cell polarity , effector , embryonic stem cell , phosphatidylinositol , neural stem cell , signal transduction , stem cell , cell , biochemistry , endoplasmic reticulum , gene
The Golgi apparatus is a central regulator of membrane trafficking and cell polarity in mammalian cells. I will discuss our recent work in a murine embryonic neural stem cell (NSC) model demonstrating that a Golgi phosphatidylinositol 4‐phosphate (PI4P)‐dependent pathway promotes loading of the Golgi system into NSC apical processes. The physiological significance of this mechanism is demonstrated by defects in apical loading of the Golgi system resulting in cell‐autonomous disruption in NSC polarity and, when imposed on a tissue‐wide scale, catastrophic failure in development of the neocortex. This pathway requires the action of a pair of phosphatidylinositol transfer proteins (PITPNA and (PITPNB) to promote PI4P production on Golgi membranes, and the actions of downstream effector proteins that respond to PI4P signaling. These effectors include GOLPH3, the nonconventional myosin Myo18A, and the ceramide transfer protein CERT. Finally, we find the PI4P‐dependent regulation of Golgi apical positioning is transmitted to the differentiated progeny of the affected NSCs and influences later steps in development of the embryonic mouse neocortex. Taken together, we have identified a novel mechanism by which PITPs, PI4P, and Golgi apparatus position regulate cell polarity and stem cell biology in the developing mammalian forebrain. Support or Funding Information This research was funded by NIH grant R01‐GM112591 and grant BE‐0017 from the Robert A. Welch Foundation. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .