Endosomal sorting complexes required for ESCRTing cells toward death during neurogenesis, neurodevelopment and neurodegeneration

• Published in: Traffic (Copenhagen, Denmark) Vol. 19; no. 7; pp. 485 - 495
• Main Authors: Kaul, Zenia, Chakrabarti, Oishee
• Format: Journal Article
• Language: English
• Published: Former Munksgaard John Wiley & Sons A/S 01-07-2018; Wiley Subscription Services, Inc
• Subjects: Apoptosis; Cell death; Cell surface; cell survival; Cytokinesis; Cytosol; ESCRTs; lysosomal blockage; mRNA; Neurodegeneration; Neurodegenerative diseases; neurodevelopment; Neurogenesis; neuronal pruning; Organelles; Proteins; RNA transport; ESCRTs; cell survival; cell death; neurodevelopment; lysosomal blockage; neurodegeneration; neurogenesis; neuronal pruning
• ISSN: 1398-9219; 1600-0854
• DOI: 10.1111/tra.12569

The endosomal sorting complexes required for transport (ESCRT) proteins help in the recognition, sorting and degradation of ubiquitinated cargoes from the cell surface, long‐lived proteins or aggregates, and aged organelles present in the cytosol. These proteins take part in the endo‐lysosomal system of degradation. The ESCRT proteins also play an integral role in cytokinesis, viral budding and mRNA transport. Many neurodegenerative diseases are caused by toxic accumulation of cargo in the cell, which causes stress and ultimately leads to neuronal death. This accumulation of cargo occurs because of defects in the endo‐lysosomal degradative pathway—loss of function of ESCRTs has been implicated in this mechanism. ESCRTs also take part in many survival processes, lack of which can culminate in neuronal cell death. While the role played by the ESCRT proteins in maintaining healthy neurons is known, their role in neurodegenerative diseases is still poorly understood. In this review, we highlight the importance of ESCRTs in maintaining healthy neurons and then suggest how perturbations in many of the survival mechanisms governed by these proteins could eventually lead to cell death; quite often these correlations are not so obviously laid out. Extensive neuronal death eventually culminates in neurodegeneration.
The endosomal sorting complexes required for transport (ESCRT) proteins instrumental in protein sorting and degradation also play essential role in the genesis, maintenance and sustenance of healthy neurons and in keeping neurodegeneration at bay. These proteins control important functions in cells like nuclear wound healing, actin remodeling, controlling the expression of calcium pumps, modulation of necroptosis, contributing in Akt survival signaling and induction of cell cycle arrest. ESCRTs control neurogenesis, regulate neurodevelopment and their loss leads to neurodegeneration.