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- Title
The Cav1.2 N terminus contains a CaM kinase site that modulates channel trafficking and function.
- Authors
Simms, Brett; Souza, Ivana; Rehak, Renata; Zamponi, Gerald
- Abstract
The L-type voltage-gated calcium channel Cav1.2 and the calcium-activated CaM kinase cascade both regulate excitation transcription coupling in the brain. CaM kinase is known to associate with the C terminus of Cav1.2 in a region called the PreIQ-IQ domain, which also binds multiple calmodulin molecules. Here we identify and characterize a second CaMKII binding site in the N terminus of Cav1.2 that is formed by a stretch of four amino residues (cysteine-isoleucine-serine-isoleucine) and which regulates channel expression and function. By using live cell imaging of tsA-201 cells we show that GFP fusion constructs of the CaMKII binding region, termed N co-localize with mCherry-CaMKII. Mutating CISI to AAAA ablates binding to and colocalization with CaMKII. Cav1.2 channels show reduced cell surface expression in tsA-201 cells, but interestingly, display an increase in channel function that offsets the trafficking deficit. Altogether our data reveal that the proximal N terminus of Cav1.2 contains a CaMKII binding region which contributes to channel surface expression and function.
- Subjects
N-terminal residues; CALCIUM-dependent protein kinase; CALCIUM channels; CASCADE connections; CYSTEINE
- Publication
Pflügers Archiv: European Journal of Physiology, 2015, Vol 467, Issue 4, p677
- ISSN
0031-6768
- Publication type
Article
- DOI
10.1007/s00424-014-1538-7