Coupled gating between intracellular calcium release channels
Principal Investigator: Andrew R. Marks, Columbia University, New York, NY, USA
International Collaborators: Karol Ondriaš, Marta Gaburjáková
Duration May 1998 – June 2006
Coordinating Organization: Columbia University, New York, NY, USA
Annotation:
The objective of the FIRCA project is to elucidate structure-function relationships of intracellular calcium release channels. In the last years important advances have been achieved in terms of identifying functional domains of the channels and in understanding the role of (FKBP12/12.6 protein in regulating function of the ryanodine receptor (RYR) that functions as a intracellular Ca2+ channel. Significant new findings and preliminary data provided by prof. A.R. Marks include: 1) FKBP12/12.6 stabilizes the RyR function in both sekeltal and cardiac muscle; 2) identification of the binding site for FKBP12/12.6 on the RYR channel; 3) RyR channels are physically bound to neighboring RYR channels and 2 or more channels can exhibit “coupled gating” in planar lipid bilayers (believed to be important for controlling excitation-contraction coupling). The proposed collaboration between the laboratories of prof. A R. Marks (Columbia University, New York, NY, USA) and dr. K. Ondrias (Slovak Academy of Sciences, Bratislava, Slovakia) should mostly cover the heterologous functional expression of ion channels and their reconstitution in artificial membrane systems.
Keywords:
Ca2+ channel, FKBP12/12.6, gen mutation, planar lipid membrane, muscle contraction, ryanodin, Sf9 cell line, T lymphocyte
Objectives:
1. Characterize coupled gating between cardiac ryanodine receptors
2. Determine whether inositol 1,4,5-trisphosphate receptors (IP3R) exhibit coupled gating
3. Determine the functional role of coupled gating between IP3R channels in T lymphocyte activation
Publications:
- Rosemblit N, Moschella MC, Ondriašová E, Gutstein DE, Ondriaš K , Marks AR (1999): Intracellular calcium release channel expression during embryogenesis. Dev Biol 206:163-177.
- Gaburjakova M, Gaburjakova J, Reiken S, Huang F, Marx SO, Rosemblit N, Marks AR (2001): FKBP12 binding modulates ryanodine receptor channel gating. J Biol Chem 276:16931-16935.
- Marx SO, Gaburjakova J, Gaburjakova M , Henrikson C, Ondrias K, Marks AR (2001): Coupled gating between cardiac calcium release channels (ryanodine receptors). Circ Res 88:1151-1158.
- DeSouza N, Reiken S, Ondrias K , Yang YM, Matkovich S, Marks AR (2002): Protein kinase A and two phosphatases are components of the inositol 1,4,5-trisphosphate receptor macromolecular signaling complex. J Biol Chem 277:39397-39400.