Nanoscale coupling of junctophilin-2 and ryanodine receptors regulates vascular smooth muscle cell contractility

作者：Harry A. T. Pritchard, Caoimhín S. Griffin, Evan Yamasaki, Pratish Thakore, Conor P. Lane, Adam Greenstein, Scott Earley · 发表于：Proceedings of the National Academy of Sciences · 年份：2019 · DOI：10.1073/pnas.1911304116 · 被引用次数：51 · 研究领域：Ion channel regulation and function、Hemoglobin structure and function、Nicotinic Acetylcholine Receptors Study

Significance The junctophilins are a family of structural proteins that organize intracellular membrane junctions, such as coupling between the endoplasmic/sarcoplasmic reticulum and plasma membrane. The junctophilins are critically important for cardiac and skeletal muscle function, but little is known about how these proteins influence vascular smooth muscle cells (SMCs). We found that one isotype, junctophilin-2 (JPH2), is abundant in SMCs and is essential for maintaining a subcellular Ca 2+ signaling pathway that is critically important for regulation of membrane potential and contractility. Our data also show that impaired expression of JPH2 results in hypercontractility of small cerebral arteries. These findings suggest that loss-of-function mutations or decreased expression of JPH2 could contribute to vascular pathologies such as systemic hypertension and vascular cognitive impairment.