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Quantitative cortical synapse proteomics of a transgenic migraine mouse model with mutated Ca V 2.1 calcium channels
Author(s) -
Klychnikov Oleg I.,
Li Ka Wan,
Sidorov Igor A.,
Loos Maarten,
Spijker Sabine,
Broos Ludo A. M.,
Frants Rune R.,
Ferrari Michel D.,
Mayboroda Oleg A.,
Deelder André M.,
Smit August B.,
van den Maagdenberg Arn M. J. M.
Publication year - 2010
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.200900733
Subject(s) - glutamatergic , familial hemiplegic migraine , synapse , biology , microbiology and biotechnology , proteomics , neurotransmission , voltage dependent calcium channel , neurite , synaptic vesicle , neuroscience , glutamate receptor , calcium , chemistry , gene , genetics , receptor , vesicle , medicine , migraine with aura , aura , migraine , organic chemistry , membrane , in vitro
Familial hemiplegic migraine type 1 (FHM1) is caused by missense mutations in the CACNA1A gene that encodes the α1A 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.