Fitxers
Tipus de document
ArticleVersió
Versió publicadaData de publicació
Tots els drets reservats
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/183703
A mutation in the first intracellular loop of CACNA1A prevents P/Q channel modulation by SNARE proteins and lowers exocytosis
Títol de la revista
Director/Tutor
ISSN de la revista
Títol del volum
Recurs relacionat
Resum
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.
Citació
Citació
SERRA, Selma A., et al. A mutation in the first intracellular loop of CACNA1A prevents P/Q channel modulation by SNARE proteins and lowers exocytosis. Proceedings of the National Academy of Sciences of the United States of America - PNAS. 2010. Vol. 107, num. 4, pags. 1672-1677. ISSN 0027-8424. [consulted: 11 of August of 2026]. Available at: https://hdl.handle.net/2445/183703