title: The role of CHMP2BIntron5in autophagy and frontotemporal dementia.
abstract: Charged multivesicular body protein 2B (CHMP2B) - a component of the endosomal complex required for transport-III (ESCRT-III) - is responsible for the vital membrane deformation functions in autophagy and endolysosomal trafficking. A dominant mutation in CHMP2B (CHMP2BIntron5) is associated with a subset of heritable frontotemporal dementia - frontotemporal dementia linked to chromosome 3 (FTD-3). ESCRT-III recruits Vps4, an AAA-ATPase that abscises the membrane during various cellular processes including autophagy and intraluminal vesicle formation. CHMP2BIntron5results in a C-terminus truncation removing an important Vps4 binding site as well as eliminating the normal autoinhibitory resting state of CHMP2B. CHMP2B is expressed in most cell types but seems to be especially vital for proper neuronal function. CHMP2BIntron5-mediated phenotypes include misregulation of transmembrane receptors, accumulation of multilamellar structures, abnormal lysosomal morphology, down regulation of a brain-specific micro RNA (miRNA-124), abnormal dendritic spine morphology, decrease in dendritic arborization, and cell death. Currently, transgenic-fly,-mouse, and -human cell lines are being used to better understand the diverse phenotypes and develop therapeutic approaches for the CHMP2BIntron5-induced FTD-3. This article is part of a Special Issue entitled SI:Autophagy.
authors.affiliation: Department of Biology, Colby College, 5720 Mayflower Hill, Waterville, ME 04901, USA.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Krasniak
authors.affiliation: Department of Biology, Colby College, 5720 Mayflower Hill, Waterville, ME 04901, USA. Electronic address: stahmad@colby.edu.
authors.forename: S Tariq
authors.initials: ST
authors.lastname: Ahmad
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics; D056827:Endosomal Sorting Complexes Required for Transport / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D057180:Frontotemporal Dementia / Q000235:genetics / Q000503:physiopathology*; D006801:Humans; D051379:Mice; D009154:Mutation; D009474:Neurons / Q000502:physiology*
chemical_list: C503812:CHMP2B protein, human; D056827:Endosomal Sorting Complexes Required for Transport
keywords: Autophagy; CHMP2B(Intron5); ESCRT-III; Endolysosome; FTD-ALS; Frontotemporal dementia