# name
A mutation in the first intracellular loop of CACNA1A prevents P/Q channel modulation by SNARE proteins and lowers exocytosis

# metadata.dc.description.abstract[].value
Familial hemiplegic migraine (FHM)-causing mutations in the gene encoding the P/Q Ca2+ channel α1A subunit (CACNA1A) locate to the pore and voltage sensor regions and normally involve gain-of-channel function. We now report on a mutation identified in the first intracellular loop of CACNA1A (α1A(A454T)) that does not cause FHM but is associated with the absence of sensorimotor symptoms in a migraine with aura pedigree. α1A(A454T) channels showed weakened regulation of voltage-dependent steady-state inactivation by CaVβ subunits. More interestingy, A454T mutation suppressed P/Q channel modulation by syntaxin 1A or SNAP-25 and decreased exocytosis. Our findings reveal the importance of I-II loop structural integrity in the functional interaction between P/Q channel and proteins of the vesicle-docking/fusion machinery, and that genetic variation in CACNA1A may be not only a cause but also a modifier of migraine phenotype.

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Proceedings of the National Academy of Sciences of the United States of America - PNAS, 2010, vol. 107, num. 4, p. 1672-1677

# metadata.dc.source[].value
Articles publicats en revistes (Genètica, Microbiologia i Estadística)

# metadata.dc.title[].value
A mutation in the first intracellular loop of CACNA1A prevents P/Q channel modulation by SNARE proteins and lowers exocytosis