Genetic deletion of Rnd3/RhoE results in mouse heart calcium leakage through upregulation of protein kinase A signaling.

ABSTRACT:

Rationale

Rnd3, a small Rho GTPase, is involved in the regulation of cell actin cytoskeleton dynamics, cell migration, and proliferation. The biological function of Rnd3 in the heart remains unexplored.

Objective

To define the functional role of the Rnd3 gene in the animal heart and investigate the associated molecular mechanism.

Methods and results

By loss-of-function approaches, we discovered that Rnd3 is involved in calcium regulation in cardiomyocytes. Rnd3-null mice died at the embryonic stage with fetal arrhythmias. The deletion of Rnd3 resulted in severe Ca(2+) leakage through destabilized ryanodine receptor type 2 Ca(2+) release channels. We further found that downregulation of Rnd3 attenuated β2-adrenergic receptor lysosomal targeting and ubiquitination, whic

SUBMITTER: Yang X 

PROVIDER: S-EPMC4282622 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature