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.

journal_name

Proteomics

journal_title

Proteomics

authors

Klychnikov OI,Li KW,Sidorov IA,Loos M,Spijker S,Broos LA,Frants RR,Ferrari MD,Mayboroda OA,Deelder AM,Smit AB,van den Maagdenberg AM

doi

10.1002/pmic.200900733

subject

Has Abstract

pub_date

2010-07-01 00:00:00

pages

2531-5

issue

13

eissn

1615-9853

issn

1615-9861

journal_volume

10

pub_type

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