title: Quantitative cortical synapse proteomics of a transgenic migraine mouse model with mutated Ca(V)2.1 calcium channels.
abstract: Familial hemiplegic migraine type 1 (FHM1) is caused by missense mutations in the CACNA1A gene that encodes the alpha1A pore-forming subunit of Ca(V)2.1 Ca(2+) channels. Knock-in (KI) transgenic mice expressing Ca(V)2.1 Ca(2+) channels with a human pathogenic FHM1 mutation reveal enhanced glutamatergic neurotransmission in the cortex. In this study, we employed an iTRAQ-based LC-LC MS/MS approach to identify differentially expressed proteins in cortical synapse proteomes of Cacna1a R192Q KI and wild-type mice. All expression differences determined were subtle and in the range of 10-30%. Observed upregulated proteins in the mutant mice are involved in processes, such as neurite outgrowth and actin dynamics, vesicle turnover, and glutamate transporters. Our data support the view that in Cacna1a R192Q KI mice, several compensatory mechanisms counterbalancing a dysregulated glutamatergic signaling have come into effect. We propose that such adaptation mechanisms at the synapse level may play a role in the pathophysiology of FHM and possibly in the common forms of migraine.
authors.affiliation: Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Oleg I
authors.initials: OI
authors.lastname: Klychnikov
authors.forename: Ka Wan
authors.initials: KW
authors.lastname: Li
authors.forename: Igor A
authors.initials: IA
authors.lastname: Sidorov
authors.forename: Maarten
authors.initials: M
authors.lastname: Loos
authors.forename: Sabine
authors.initials: S
authors.lastname: Spijker
authors.forename: Ludo A M
authors.initials: LA
authors.lastname: Broos
authors.forename: Rune R
authors.initials: RR
authors.lastname: Frants
authors.forename: Michel D
authors.initials: MD
authors.lastname: Ferrari
authors.forename: Oleg A
authors.initials: OA
authors.lastname: Mayboroda
authors.forename: André M
authors.initials: AM
authors.lastname: Deelder
authors.forename: August B
authors.initials: AB
authors.lastname: Smit
authors.forename: Arn M J M
authors.initials: AM
authors.lastname: van den Maagdenberg
mesh_terms: D000818:Animals; D020864:Calcium Channels, N-Type / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D051379:Mice; D008822:Mice, Transgenic; D008881:Migraine Disorders / Q000378:metabolism*; D009154:Mutation; D040901:Proteomics; D015398:Signal Transduction; D013569:Synapses / Q000737:chemistry* / Q000378:metabolism
chemical_list: D020864:Calcium Channels, N-Type