The role of CHMP2B in frontotemporal dementia

Biochem Soc Trans. 2009 Feb;37(Pt 1):208-12. doi: 10.1042/BST0370208.

Abstract

Mutations in the CHMP2B (charged multivesicular body protein 2B) gene that lead to C-terminal truncations of the protein can cause frontotemporal dementia. CHMP2B is a member of ESCRT-III (endosomal sorting complex required for transport III), which is required for formation of the multivesicular body, a late endosomal structure that fuses with the lysosome to degrade endocytosed proteins. Overexpression of mutant C-terminally truncated CHMP2B proteins produces an enlarged endosomal phenotype in PC12 and human neuroblastoma cells, which is likely to be due to a dominant-negative effect on endosomal function. Disruption of normal endosomal trafficking is likely to affect the transport of neuronal growth factors and autophagic clearance of proteins, both of which could contribute to neurodegeneration in frontotemporal dementia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alternative Splicing / genetics
  • Amino Acid Sequence
  • Animals
  • Autophagy
  • Dementia / genetics
  • Dementia / metabolism*
  • Dementia / pathology
  • Endosomes / metabolism
  • Humans
  • Molecular Sequence Data
  • Nerve Growth Factors / metabolism
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*

Substances

  • Nerve Growth Factors
  • Nerve Tissue Proteins