Characterization of Cav1.4 Complexes (α11.4, β2, and α2δ4) in HEK293T Cells and in the Retina

作者: Amy Lee , Shiyi Wang , Brittany Williams , Jussara Hagen , Todd E. Scheetz

DOI: 10.1074/JBC.M114.607465

关键词:

摘要: In photoreceptor synaptic terminals, voltage-gated Cav1.4 channels mediate Ca(2+) signals required for transmission of visual stimuli. Like other high voltage-activated Cav channels, are composed a main pore-forming α1 subunit and auxiliary β α2δ subunits. Of the four distinct classes α2δ, β2 α2δ4 thought to co-assemble with subunits in photoreceptors. However, an understanding functional properties this combination is lacking. Here, we provide evidence that α1, β2, contribute channel complexes retina describe their electrophysiological recordings. addition, identified variant named here β2X13, which, along β2a, present terminals. were coimmunoprecipitated from lysates transfected HEK293 cells mouse found interact outer plexiform layer containing by proximity ligation assays. whole-cell patch clamp recordings HEK293T cells, (Cav1.4 + β2X13) exhibited weaker voltage-dependent activation than those α2δ1. Moreover, compared α2δ4) β2X13-containing greater inactivation. The latter effect was specific because it not seen Cav1.2 channels. Our results first detailed analysis form native indicate potential heterogeneity these conferred β2a β2X13 variants.

参考文章(72)
Greg L. Lyford, Peter R. Strege, Allan Shepard, Yijun Ou, Leonid Ermilov, Steven M. Miller, Simon J. Gibbons, James L. Rae, Joseph H. Szurszewski, Gianrico Farrugia, α1C (Cav1.2) L-type calcium channel mediates mechanosensitive calcium regulation American Journal of Physiology-cell Physiology. ,vol. 283, ,(2002) , 10.1152/AJPCELL.00140.2002
S. BOLTE, F. P. CORDELIÈRES, A guided tour into subcellular colocalization analysis in light microscopy Journal of Microscopy. ,vol. 224, pp. 213- 232 ,(2006) , 10.1111/J.1365-2818.2006.01706.X
A. Davies, I. Kadurin, A. Alvarez-Laviada, L. Douglas, M. Nieto-Rostro, C. S. Bauer, W. S. Pratt, A. C. Dolphin, The alpha2delta subunits of voltage-gated calcium channels form GPI-anchored proteins, a posttranslational modification essential for function. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 107, pp. 1654- 1659 ,(2010) , 10.1073/PNAS.0908735107
Dipayan Chaudhuri, John B. Issa, David T. Yue, Elementary mechanisms producing facilitation of Cav2.1 (P/Q-type) channels. The Journal of General Physiology. ,vol. 129, pp. 385- 401 ,(2007) , 10.1085/JGP.200709749
Fiona Mansergh, Noelle C. Orton, John P. Vessey, Melanie R. Lalonde, William K. Stell, Francois Tremblay, Steven Barnes, Derrick E. Rancourt, N. Torben Bech-Hansen, Mutation of the calcium channel gene Cacna1f disrupts calcium signaling, synaptic transmission and cellular organization in mouse retina Human Molecular Genetics. ,vol. 14, pp. 3035- 3046 ,(2005) , 10.1093/HMG/DDI336
Katharina A. Wycisk, Birgit Budde, Silke Feil, Sergej Skosyrski, Francesca Buzzi, John Neidhardt, Esther Glaus, Peter Nu¨rnberg, Klaus Ruether, Wolfgang Berger, Structural and functional abnormalities of retinal ribbon synapses due to Cacna2d4 mutation. Investigative Ophthalmology & Visual Science. ,vol. 47, pp. 3523- 3530 ,(2006) , 10.1167/IOVS.06-0271
Alejandro Sandoval, Norma Oviedo, Arturo Andrade, Ricardo Felix, Glycosylation of asparagines 136 and 184 is necessary for the α2δ subunit-mediated regulation of voltage-gated Ca2+ channels FEBS Letters. ,vol. 576, pp. 21- 26 ,(2004) , 10.1016/J.FEBSLET.2004.08.054
Diane Lipscombe, Arturo Andrade, Summer E. Allen, Alternative splicing: Functional diversity among voltage-gated calcium channels and behavioral consequences Biochimica et Biophysica Acta. ,vol. 1828, pp. 1522- 1529 ,(2013) , 10.1016/J.BBAMEM.2012.09.018
Dana Specht, Shu-Biao Wu, Paul Turner, Peter Dearden, Frank Koentgen, Uwe Wolfrum, Marion Maw, Johann Helmut Brandsta¨tter, Susanne tom Dieck, Effects of presynaptic mutations on a postsynaptic Cacna1s calcium channel colocalized with mGluR6 at mouse photoreceptor ribbon synapses. Investigative Ophthalmology & Visual Science. ,vol. 50, pp. 505- 515 ,(2009) , 10.1167/IOVS.08-2758
W. ROWLAND TAYLOR, CATHERINE MORGANS, Localization and properties of voltage-gated calcium channels in cone photoreceptors of Tupaia belangeri Visual Neuroscience. ,vol. 15, pp. 541- 552 ,(1998) , 10.1017/S0952523898153142