In:
Science, American Association for the Advancement of Science (AAAS), Vol. 362, No. 6421 ( 2018-12-21), p. 1359-1360
Abstract:
The heart pumps blood to the rest of the body in a coordinated and steadfast manner. This pumping function is achieved through synchronous contraction of billions of cardiomyocytes (heart muscle cells), which is governed by phasic increases in intracellular calcium. As such, cardiomyocytes have evolved intricate cellular structures that tightly couple external electrical impulses to the triggering of calcium ion release from intracellular stores and subsequent activation of force-producing proteins, a process termed excitation-contraction (E-C) coupling. A key component of this molecular ultrastructure is the cardiac dyad, a microdomain that juxtaposes the plasma membrane L-type calcium channel with the calcium-sensitive ryanodine receptor (RyR) channel complex, the molecular gatekeeper for the release of calcium ions from sarcoplasmic reticulum stores in cardiomyocytes. The cardiac dyad is physically stabilized by a membrane-associated scaffold protein called junctophilin-2 (JP2), which facilitates physiologic calcium release during E-C coupling. Excessive stress or injury to cardiomyocytes results in defective E-C coupling, reduced pumping capacity, and the clinical syndrome of heart failure, a leading cause of death worldwide. On page 1375 of this issue, Guo et al. ( 1 ) report the surprising discovery that during cardiac stress, a proteolytically cleaved fragment of JP2 can translocate to the cardiomyocyte nucleus and function as a transcription factor that can protect against heart failure pathogenesis. Thus, in addition to its “day job” as a structural protein, this suggest that JP2 can “moonlight” in the nucleus as part of a homeostatic feedback response to cardiac stress.
Type of Medium:
Online Resource
ISSN:
0036-8075
,
1095-9203
DOI:
10.1126/science.aav8956
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2018
detail.hit.zdb_id:
128410-1
detail.hit.zdb_id:
2066996-3
detail.hit.zdb_id:
2060783-0
SSG:
11
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