Molecular mechanism of TMEM16A regulation: role of CaMKII and PP1/PP2A.

This study explored the mechanism by which Ca-activated Cl channels (CaCCs) encoded by the gene are regulated by calmodulin-dependent protein kinase II (CaMKII) and protein phosphatases 1 (PP1) and 2A (PP2A). Ca-activated Cl currents () were recorded from HEK-293 cells expressing mouse TMEM16A. were evoked using a pipette solution in which free Ca concentration was clamped to 500 nM, in the presence (5 mM) or absence of ATP.

Knockdown of subunit 3 of the COP9 signalosome inhibits C2C12 myoblast differentiation via NF-KappaB signaling pathway.

Background: The COP9 signalosome (CSN) is a conserved protein complex composed of 8 subunits designated CSN1-CSN8. CSN3 represents the third subunit of the CSN and maintains the integrity of the complex. CSN3 binds to the striated muscle-specific β1D integrin tail, and its subcellular localization is altered in differentiated skeletal muscle cells.

Insulin-like growth factors and their potential role in cardiac epigenetics.

Cardiovascular disease (CVD) constitutes a major public health threat worldwide, accounting for 17.3 million deaths annually. Heart disease and stroke account for the majority of healthcare costs in the developed world.

Inhibition of Aβ oligomerization in yeast by a PICALM ortholog and certain FDA approved drugs.

The formation of small Aβ oligomers has been implicated as a toxic species in Alzheimer disease (AD). In strong support of this hypothesis we found that overexpression of Yap1802, the yeast ortholog of the human AD risk factor, phosphatidylinositol binding clathrin assembly protein (PICALM), reduced oligomerization of Aβ fused to a reporter in yeast. Thus we used the Aβ-reporter system to identify drugs that could be developed into therapies that prevent or arrest AD.

Molecular and functional significance of Ca(2+)-activated Cl(-) channels in pulmonary arterial smooth muscle.

Increased peripheral resistance of small distal pulmonary arteries is a hallmark signature of pulmonary hypertension (PH) and is believed to be the consequence of enhanced vasoconstriction to agonists, thickening of the arterial wall due to remodeling, and increased thrombosis. The elevation in arterial tone in PH is attributable, at least in part, to smooth muscle cells of PH patients being more depolarized and displaying higher intracellular Ca(2+) levels than cells from normal subjects. It is now clear that downregulation of voltage-dependent K(+) channels (e.