Palmitoylation of BMPR1a regulates neural stem cell fate

  • Proc Natl Acad Sci U S A. 2019 Dec 17;116(51):25688-25696. doi: 10.1073/pnas.1912671116.
Thomas Wegleiter  1 ,  Kilian Buthey  2 ,  Daniel Gonzalez-Bohorquez  2 ,  Martina Hruzova  2 ,  Muhammad Khadeesh Bin Imtiaz  2 ,  Andrin Abegg  2 ,  Iliana Mebert  2 ,  Adriano Molteni  2 ,  Dominik Kollegger  2 ,  Pawel Pelczar  3 ,  Sebastian Jessberger  1
Affiliations
  • 1. Laboratory of Neural Plasticity, Faculties of Medicine and Science, Brain Research Institute, University of Zurich, 8057 Zurich, Switzerland; [email protected] [email protected].
  • 2. Laboratory of Neural Plasticity, Faculties of Medicine and Science, Brain Research Institute, University of Zurich, 8057 Zurich, Switzerland.
  • 3. Center for Transgenic Models, University of Basel, 4001 Basel, Switzerland.
PMID: 31772009 DOI: 10.1073/pnas.1912671116
Abstract

Neural stem cells (NSCs) generate neurons and glial cells throughout embryonic and postnatal brain development. The role of S-palmitoylation (also referred to as S-acylation), a reversible posttranslational lipid modification of proteins, in regulating the fate and activity of NSCs remains largely unknown. We used an unbiased screening approach to identify proteins that are S-acylated in mouse NSCs and showed that bone morphogenic protein receptor 1a (BMPR1a), a core mediator of BMP signaling, is palmitoylated. Genetic manipulation of S-acylated sites affects the localization and trafficking of BMPR1a and leads to altered BMP signaling. Strikingly, defective palmitoylation of BMPR1a modulates NSC function within the mouse brain, resulting in enhanced oligodendrogenesis. Thus, we identified a mechanism regulating the behavior of NSCs and provided the framework to characterize dynamic posttranslational lipid modifications of proteins in the context of NSC biology.

Keywords
BMP receptor; neural stem cell; neurogenesis; oligodendrogenesis; palmitoylation.
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