Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/183703
Title: | A mutation in the first intracellular loop of CACNA1A prevents P/Q channel modulation by SNARE proteins and lowers exocytosis |
Author: | Serra, Selma A. Cuenca León, Ester Llobet Berenguer, Artur, 1972- Rubio-Moscardo, Francisca Plata, Cristina Carreño, Oriel Fernàndez Castillo, Noèlia Corominas Castiñeira, Roser Valverde, Miguel A. Macaya, Alfons Cormand Rifà, Bru Fernández-Fernández, José M. |
Keywords: | Migranya Genètica Migraine Genetics |
Issue Date: | 2010 |
Publisher: | National Academy of Sciences |
Abstract: | 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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1073/pnas.0908359107 |
It is part of: | Proceedings of the National Academy of Sciences of the United States of America - PNAS, 2010, vol. 107, num. 4, p. 1672-1677 |
URI: | http://hdl.handle.net/2445/183703 |
Related resource: | https://doi.org/10.1073/pnas.0908359107 |
ISSN: | 0027-8424 |
Appears in Collections: | Articles publicats en revistes (Patologia i Terapèutica Experimental) Articles publicats en revistes (Genètica, Microbiologia i Estadística) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
588222.pdf | 753.67 kB | Adobe PDF | View/Open |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.