STAT3: a link between CaMKII–βIV-spectrin and maladaptive remodeling?
Mohit Hulsurkar, Ann P. Quick, Xander H.T. Wehrens
Mohit Hulsurkar, Ann P. Quick, Xander H.T. Wehrens
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Commentary

STAT3: a link between CaMKII–βIV-spectrin and maladaptive remodeling?

Abstract

βIV-Spectrin, along with ankyrin and Ca2+/calmodulin-dependent kinase II (CaMKII), has been shown to form local signaling domains at the intercalated disc, while playing a key role in the regulation of Na+ and K+ channels in cardiomyocytes. In this issue of the JCI, Unudurthi et al. show that under chronic pressure overload conditions, CaMKII activation leads to βIV-spectrin degradation, resulting in the release of sequestered STAT3 from the intercalated discs. This in turn leads to dysregulation of STAT3-mediated gene transcription, maladaptive remodeling, fibrosis, and decreased cardiac function. Overall, this study presents interesting findings regarding the role of CaMKII and βIV-spectrin under physiological as well as pathological conditions.

Authors

Mohit Hulsurkar, Ann P. Quick, Xander H.T. Wehrens

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Figure 1

Schematic of the CaMKII/βIV-spectrin signaling axis at the cell membrane.

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Schematic of the CaMKII/βIV-spectrin signaling axis at the cell membrane...
CaMKII and βIV-spectrin bind to ankyrin-G (AnkG) and multiple ion channels such as Kir6.2 and Nav1.5 in the plasma membrane. In the present study, Unudurthi et al. show that, upon being phosphorylated by CaMKII, βIV-spectrin is degraded, which leads to STAT3 release and translocation into the nucleus, activating gene transcription in response to chronic stress. Some of the unanswered questions for future studies are highlighted in the black boxes in the figure.