title: Membrane topology and membrane retention of the ryanodine receptor calcium release channel.
abstract: The ryanodine receptor (RyR) is a Ca2+ release channel located in the sarcoplasmic/endoplasmic reticulum (ER) membrane and plays a critical role in excitation-contraction coupling of skeletal and cardiac muscles. RyR normally exists in a tetrameric structure and contains two functional domains: a carboxyl-terminal hydrophobic domain that contains the conduction pore of the Ca2+ release channel, and a large amino-terminal domain that contains sites responsible for channel regulation. Recent studies involving mutagenesis and heterologous expression have helped unravel the structure-function relationship of RyR, including transmembrane topology and intracellular localization of the Ca2+-release channel. The carboxyl-terminal portion of RyR contains the putative transmembrane segments and is sufficient to form a functional Ca2+-release channel. The amino-terminal region of the protein contains sites responsible for regulation by endogenous modulators such as Ca2+ and Mg2+ and by exogenous ligands such as caffeine. The membrane topology of RyR appears to contain an even number (four or six) of transmembrane segments with a ion selectivity filter present within a region residing between the last two segments, similar to potassium channel, whose atomic structure was described recently. The transmembrane segments also contain sequences that are responsible for localization of RyR in the endoplasmic reticulum, and this sequence is highly conserved in IP3 receptors, which also function as Ca2+-release channels.
authors.affiliation: Department of Physiology and Biophysics, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA. maj2@umdnj.edu
authors.forename: Jianjie
authors.initials: J
authors.lastname: Ma
authors.forename: Salim M
authors.initials: SM
authors.lastname: Hayek
authors.forename: Manjunatha B
authors.initials: MB
authors.lastname: Bhat
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000737:chemistry / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D002462:Cell Membrane / Q000737:chemistry / Q000502:physiology*; D006321:Heart / Q000502:physiology*; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D008560:Membrane Fluidity / Q000502:physiology; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000502:physiology*; D009200:Myocardial Contraction; D019837:Ryanodine Receptor Calcium Release Channel / Q000737:chemistry* / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium