The importance of occupancy rather than affinity of CaV(beta) subunits for the calcium channel I-II linker in relation to calcium channel function.

The Journal of Physiology
Adrian J ButcherAnnette C Dolphin

Abstract

The Ca(V)beta subunits of voltage-gated calcium channels regulate the trafficking and biophysical properties of these channels. We have taken advantage of mutations in the tyrosine residue within the alpha interaction domain (AID) in the I-II linker of Ca(V)2.2 which reduce, but do not abolish, the binding of beta1b to the AID of Ca(V)2.2. We have found that the mutation Y388S decreased the affinity of Ca(V)beta1b binding to the Ca(V)2.2 I-II linker from 14 to 329 nm. However, the Y388S mutation had no effect on current density and cell surface expression of Ca(V)2.2/alpha2delta-2/beta1b channels expressed in human embryonic kidney tsA-201 cells, when equivalent proportions of cDNA were used. Furthermore, despite the 24-fold reduced affinity of Ca(V)beta1b for the Y388S I-II linker of Ca(V)2.2, all the key features of modulation as well as trafficking by Ca(V)beta subunits remained intact. This is in contrast to the much more marked effect of the W391A mutation, which abolished interaction with the Ca(V)2.2 I-II linker, and very markedly affected the trafficking of the channels. However, using the Xenopus oocyte expression system, where expression levels can be accurately titrated, when Ca(V)beta1b cDNA was diluted 50-fold, all...Continue Reading

References

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Citations

Jul 25, 2008·Pflügers Archiv : European journal of physiology·Andriy V DresviannikovAnnette C Dolphin
May 19, 2010·The Journal of Biological Chemistry·Benoîte BourdinLucie Parent
Oct 26, 2018·Proceedings of the National Academy of Sciences of the United States of America·Xingjuan ChenSamy O Meroueh
Dec 13, 2007·Journal of Molecular Recognition : JMR·Rebecca L Rich, David G Myszka
Jul 13, 2011·The Journal of Physiology·Kun Fang, Henry M Colecraft
Oct 21, 2010·Physiological Reviews·Zafir Buraei, Jian Yang
Oct 21, 2006·Biochemical Society Transactions·F Van Petegem, D L Minor
Sep 28, 2018·Proceedings of the National Academy of Sciences of the United States of America·Jun-Hee YeonByung-Chang Suh
Feb 22, 2007·Journal of Cell Science·David J LoaneNeil V Marrion
Sep 18, 2012·Biochimica Et Biophysica Acta·Zafir Buraei, Jian Yang

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