Phosphatidylinositol (3,5)-bisphosphate machinery regulates neurite thickness through neuron-specific endosomal protein NSG1/NEEP21.

ABSTRACT: Phosphatidylinositol (3,5)-bisphosphate [PtdIns(3,5)P₂] is a critical signaling phospholipid involved in endolysosome homeostasis. It is synthesized by a protein complex composed of PIKfyve, Vac14, and Fig4. Defects in PtdIns(3,5)P₂ synthesis underlie a number of human neurological disorders, including Charcot-Marie-Tooth disease, child onset progressive dystonia, and others. However, neuron-specific functions of PtdIns(3,5)P₂ remain less understood. Here, we show that PtdIns(3,5)P₂ pathway is required to maintain neurite thickness. Suppression of PIKfyve activities using either pharmacological inhibitors or RNA silencing resulted in decreased neurite thickness. We further find that the regulation of neurite thickness by PtdIns(3,5)P₂

SUBMITTER: Qi L 

PROVIDER: S-EPMC9823133 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature