| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Abrams, Jeffrey Wan, Elaine Yang, Lin Samad, Tahmina Weinberg, Richard L. Marx, Steven O. Katchman, Alexander Pitt, Geoffrey S. |
| Description |
Author Affiliation: Yang L ( From the Division of Cardiology, Departments of Medicine and Pharmacology, College of Physicians and Surgeons, Columbia University, New York, New York 10032 and.); Katchman A ( From the Division of Cardiology, Departments of Medicine and Pharmacology, College of Physicians and Surgeons, Columbia University, New York, New York 10032 and.); Weinberg RL ( From the Division of Cardiology, Departments of Medicine and Pharmacology, College of Physicians and Surgeons, Columbia University, New York, New York 10032 and.); Abrams J ( From the Division of Cardiology, Departments of Medicine and Pharmacology, College of Physicians and Surgeons, Columbia University, New York, New York 10032 and.); Samad T ( From the Division of Cardiology, Departments of Medicine and Pharmacology, College of Physicians and Surgeons, Columbia University, New York, New York 10032 and.); Wan E ( From the Division of Cardiology, Departments of Medicine and Pharmacology, College of Physicians and Surgeons, Columbia University, New York, New York 10032 and.); Pitt GS ( the Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.); Marx SO ( From the Division of Cardiology, Departments of Medicine and Pharmacology, College of Physicians and Surgeons, Columbia University, New York, New York 10032 and sm460@columbia.edu.) |
| Abstract |
Voltage-gated Ca(2+) channels play a key role in initiating muscle excitation-contraction coupling, neurotransmitter release, gene expression, and hormone secretion. The association of CaV1.2 with a supramolecular complex impacts trafficking, localization, turnover, and, most importantly, multifaceted regulation of its function in the heart. Several studies hint at an important role for the C terminus of the 1C subunit as a hub for multidimensional regulation of CaV1.2 channel trafficking and function. Recent studies have demonstrated an important role for the four-residue PDZ binding motif at the C terminus of 1C in interacting with scaffold proteins containing PDZ domains, in the subcellular localization of CaV1.2 in neurons, and in the efficient signaling to cAMP-response element-binding protein in neurons. However, the role of the 1C PDZ ligand domain in the heart is not known. To determine whether the 1C PDZ motif is critical for CaV1.2 trafficking and function in cardiomyocytes, we generated transgenic mice with inducible expression of an N-terminal FLAG epitope-tagged dihydropyridine-resistant 1C with the PDZ motif deleted (ΔPDZ). These mice were crossed with -myosin heavy chain reverse transcriptional transactivator transgenic mice, and the double-transgenic mice were fed doxycycline. The ΔPDZ channels expressed, trafficked to the membrane, and supported robust excitation-contraction coupling in the presence of nisoldipine, a dihydropyridine Ca(2+) channel blocker, providing functional evidence that they appropriately target to dyads. The ΔPDZ Ca(2+) channels were appropriately regulated by isoproterenol and forskolin. These data indicate that the 1C PDZ motif is not required for surface trafficking, localization to the dyad, or adrenergic stimulation of CaV1.2 in adult cardiomyocytes. |
| ISSN |
00219258 |
| e-ISSN |
1083351X |
| Journal |
Journal of Biological Chemistry |
| Issue Number |
4 |
| Volume Number |
290 |
| Language |
English |
| Publisher |
American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date |
2015-01-23 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Calcium Channels, L-Type Chemistry Physiology Heart Myocardium Metabolism Myocytes, Cardiac Amino Acid Motifs Animals Calcium Channel Blockers Colforsin Epitopes Gene Deletion Ligands Mice Mice, Transgenic Neurons Nisoldipine Protein Structure, Tertiary Rabbits Surface Properties Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Cell Biology Biochemistry Molecular Biology |
