Rabbit Anti-Human CHMP2B (a.a. 31-120) Polyclonal antibody

The endosomal sorting complex required for transport (ESCRT) is made of subcomplexes (ESCRT 0-III), crucial to membrane remodelling at endosomes, nuclear envelope and cell surface. ESCRT-III shapes membranes and in most cases cooperates with the ATPase VPS4 to mediate fission of membrane necks from the inside. The first ESCRT complexes mainly serve to catalyse the formation of ESCRT-III but can be bypassed by accessory proteins like the Alg-2 interacting protein-X (ALIX). In the nervous system, ALIX/ESCRT controls the survival of embryonic neural progenitors and later on the outgrowth and pruning of axons and dendrites, all necessary steps to establish a functional brain. In the adult brain, ESCRTs allow the endosomal turn over of synaptic vesicle proteins while stable ESCRT complexes might serve as scaffolds for the postsynaptic parts. The necessity of ESCRT for the harmonious function of the brain has its pathological counterpart, the mutations in CHMP2B of ESCRT-III giving rise to several neurodegenerative diseases. (c) 2017 Published by Elsevier Ltd.

ESCRT (endosomal sorting complex required for transport) proteins were originally identified for their role in delivering endocytosed proteins to the intraluminal vesicles of late endosomal structures termed multivesicular bodies Multivesicular bodies then fuse with lysosomes leading to degradation of the internalized proteins Four ESCRT complexes interact to concentrate cargo on the endosomal membrane induce membrane curvature to form an intraluminal bud and finally pinch off the bud through a membrane scission event to produce the intraluminal vesicle Recent work suggests that ESCRT proteins are also required downstream of these events to enable fusion of multivesicular bodies with lysosomes Autophagy is a related pathway required for the degradation of organelles long lived proteins and protein aggregates which also converges on lysosomes The proteins or organelle to be degraded are encapsulated by an autophagosome that fuses either directly with a lysosome or with an endosome to form an amphisome which then fuses with a lysosome A common machinery is beginning to emerge that regulates fusion events in the multivesicular body and autophagy pathways and we focus in the present paper on the role of ESCRT proteins These fusion events have been implicated in diseases including frontotemporal dementia Alzheimers disease lysosomal storage disorders myopathies and bacterial pathogen invasion and therefore further examination of the mechanisms involved may lead to new insight into disease pathogenesis and treatments