Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10802425 | Biochimica et Biophysica Acta (BBA) - Molecular Cell Research | 2013 | 13 Pages |
Abstract
RTN1A is a reticulon protein with predominant localization in the endoplasmic reticulum (ER). It was previously shown that RTN1A is expressed in neurons of the mammalian central nervous system but functional information remains sparse. To elucidate the neuronal function of RTN1A, we chose to focus our investigation on identifying possible novel binding partners specifically interacting with the unique N-terminus of RTN1A. Using a nonbiased approach involving GST pull-downs and MS analysis, we identified the intracellular calcium release channel ryanodine receptor 2 (RyR2) as a direct binding partner of RTN1A. The RyR2 binding site was localized to a highly conserved 150-amino acid residue region. RTN1A displays high preference for RyR2 binding in vitro and in vivo and both proteins colocalize in hippocampal neurons and Purkinje cells. Moreover, we demonstrate the precise subcellular localization of RTN1A in Purkinje cells and show that RTN1A inhibits RyR channels in [3H]ryanodine binding studies on brain synaptosomes. In a functional assay, RTN1A significantly reduced RyR2-mediated Ca2Â + oscillations. Thus, RTN1A and RyR2 might act as functional partners in the regulation of cytosolic Ca2Â + dynamics the in neurons.
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Authors
Levent Kaya, Barbara Meissner, Maria Christine Riedl, Martin Muik, Christoph Schwarzer, Francesco Ferraguti, Bettina Sarg, Herbert Lindner, Rüdiger Schweigreiter, Hans-Günther Knaus, Christoph Romanin, Christine E. Bandtlow,