Toxicity and endocytosis of spinocerebellar ataxia type 6 polyglutamine domains: Role of myosin IIB
type: Dataset
description: Spinocerebellar ataxia type 6 (SCA6) is a dominantly inherited neurodegenerative disease caused by a small expansion of CAG repeats in the sequence coding for the cytoplasmic C-terminal region of the Ca(v)2.1 subunit of P/Q-type calcium channels. We have tested the toxicity of mutated Ca(v)2.1 C-terminal domains expressed in the plasma membrane. In COS-7 cells, CD4-green fluorescent protein fused to Ca(v)2.1 C-terminal domains containing expanded 24 polyglutamine (Q) tracts displayed increased toxicity and stronger expression at the cell surface relative to 'normal' 12 Q tracts, partially because of reduced endocytosis. Glutathione S-transferase pull-down and proteomic analysis indicated that Ca(v)2.1 C-termini interact with the heavy and light chains of cerebellar myosin IIB, a molecular motor protein. This interaction was confirmed by coimmunoprecipitation from rat cerebellum and COS-7 cells and shown to be direct by binding of in vitro-translated S-35-myosin IIB heavy chain. In COS-7 cells, incremented polyglutamine tract length increased the interaction with myosin IIB. Furthermore, the myosin II inhibitor blebbistatin reversed the effects of polyglutamine expansion on plasma membrane expression. Our findings suggest a key role of myosin IIB in promoting accumulation of mutant Ca(v)2.1Ct at the plasma membrane and suggest that this gain of function might contribute to the pathogenesis of SCA6.
landing page: 1398-9219
keyword: alpha1a-voltage-dependent-calcium-channel
keyword: association
keyword: brain
keyword: cag-repeat
keyword: calcium-channels
keyword: cell-toxicity
keyword: complex
keyword: exocytosis
keyword: expression
keyword: huntingtons-disease
keyword: infoeu-reposemanticsarticle
keyword: journal-articles
keyword: myosin
keyword: neurodegeneration
keyword: neurodegenerative-disease
keyword: receptor-trafficking
keyword: sca6
keyword: scconeurcognitive-scienceneuroscience
keyword: spinocerebellar-ataxia
issued: 2026-05-15T15:32:15.676479
modified: 2026-05-15T15:32:15.676485
language: en
contact point: Organization
  fn: CCSD

test_moissonnage_selune
type: Agent

Toxicity and endocytosis of spinocerebellar ataxia type 6 polyglutamine domains: Role of myosin IIB
type: Distribution
format: HTML
access URL: https://hal.science/hal-00709920
issued: 2026-05-15T15:32:15.762718
modified: 2026-05-15T15:32:15.639594