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Calcium channel γ subunits: a functionally diverse protein family

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Abstract

The calcium channel γ subunits comprise an eight-member protein family that share a common topology consisting of four transmembrane domains and intracellular N- and C-termini. Although the first γ subunit was identified as an auxiliary subunit of a voltage-dependent calcium channel, a review of phylogenetic, bioinformatic, and functional studies indicates that they are a functionally diverse protein family. A cluster containing γ1 and γ6 conforms to the original description of the protein family as they seem to act primarily as subunits of calcium channels expressed in muscle. Members of a second cluster (γ2, γ3, γ4, γ8) function as regulators of AMPA receptor localization and function in the brain and are collectively known as TARPs. The function of members of the third cluster (γ5, γ7) remains unclear. Our analysis shows that the members of each cluster contain conserved regulatory motifs that help to differentiate the groups. However, the physiological significance of these motifs in many cases remains to be demonstrated.

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Notes

  1. Published protein sequences of γ subunits and claudins were retrieved from NCBI protein database (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein). The sequence accession numbers and chromosomal locations of γ genes used in this article are available in Tables 1 and 2, respectively. The hydropathy plot and transmembrane topology of γs were taken directly from Chu et al. [13]. The transmembrane topology of claudins was predicted by TMHMM program v2.0 (http://www.cbs.dtu.dk/services/TMHMM/). Multiple sequence alignments were performed using ClustalW at default settings (http://www.ebi.ac.uk/clustalw/index.html). Putative functional sites in each sequence were identified in the online PROSITE database ([26], http://ca.expasy.org/prosite). Since no consensus motif of palmitoylation sites has been defined [48], in silico predictions based on experimental data in the literature were used to scan claudins and γs with the cut-off value of 2.6 [57].

Abbreviations

AMPA:

α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid

LVA/HVA :

low-/high-voltage activated

PDZ:

PSD-95/DLG/ZO-1

PKC:

protein kinase C

PKA/G:

cAMP/cGMP-dependent protein kinase

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Authors and Affiliations

  1. Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, 524 Burrill Hall, MC-114, 407 S Goodwin Ave., Urbana, IL, 61801, USA

    Ren-Shiang Chen, Tzyy-Chyn Deng, Thomas Garcia, Zachary M. Sellers & Philip M. Best

  2. College of Medicine, University of Illinois at Urbana-Champaign, 524 Burrill Hall, MC-114, 407 S Goodwin Ave., Urbana, IL, 61801, USA

    Zachary M. Sellers & Philip M. Best

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Chen, RS., Deng, TC., Garcia, T. et al. Calcium channel γ subunits: a functionally diverse protein family. Cell Biochem Biophys 47, 178–186 (2007). https://doi.org/10.1007/s12013-007-0002-0

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