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Palmitoylation of BMPR1a regulates neural stem cell fate.


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.

SUBMITTER: Wegleiter T 

PROVIDER: S-EPMC6926058 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Palmitoylation of BMPR1a regulates neural stem cell fate.

Wegleiter Thomas T   Buthey Kilian K   Gonzalez-Bohorquez Daniel D   Hruzova Martina M   Bin Imtiaz Muhammad Khadeesh MK   Abegg Andrin A   Mebert Iliana I   Molteni Adriano A   Kollegger Dominik D   Pelczar Pawel P   Jessberger Sebastian S  

Proceedings of the National Academy of Sciences of the United States of America 20191126 51


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, i  ...[more]

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