CHMP2B

CHMP2B

CHMP2B is a protein that in humans is encoded by the CHMP2B gene. It is a member of the charged multivesicular body protein (CHMP) family, which is involved in the endosomal sorting complex required for transport (ESCRT) pathway. This pathway is crucial for the sorting of ubiquitinated proteins into multivesicular bodies (MVBs), which are then delivered to lysosomes for degradation.

Structure

CHMP2B is a component of the ESCRT-III complex, which is responsible for the final stages of the MVB sorting pathway. The protein is composed of several coiled-coil domains that facilitate its interaction with other ESCRT-III components. The structure of CHMP2B allows it to polymerize into filaments that are essential for membrane scission events during the formation of MVBs.

Function

The primary function of CHMP2B is to participate in the ESCRT-III complex, which is involved in the budding of vesicles into the lumen of the MVB. This process is critical for the degradation of membrane proteins and the regulation of various cellular processes, including receptor downregulation, virus budding, and cytokinesis.

Clinical Significance

Mutations in the CHMP2B gene have been linked to several neurodegenerative disorders, most notably frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). These mutations can lead to the production of aberrant CHMP2B proteins that disrupt normal ESCRT-III function, resulting in impaired protein degradation and cellular homeostasis.

Frontotemporal Dementia

Frontotemporal dementia is a form of dementia characterized by progressive neuronal loss predominantly in the frontal and temporal lobes of the brain. Mutations in CHMP2B have been identified in familial cases of FTD, suggesting a genetic component to the disease. The exact mechanism by which CHMP2B mutations lead to FTD is still under investigation, but it is believed to involve the accumulation of toxic protein aggregates due to impaired autophagic and endosomal pathways.

Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis is a neurodegenerative disease that affects motor neurons, leading to muscle weakness and atrophy. Similar to FTD, CHMP2B mutations have been implicated in some familial cases of ALS. The disruption of normal ESCRT-III function by mutant CHMP2B proteins is thought to contribute to the pathogenesis of ALS by affecting neuronal survival and function.

Also see

• ESCRT complex
• Multivesicular body
• Protein degradation
• Neurodegenerative disorders