Ion channels in glomerular mesangial cells from humans, rats, and mice have been studied by electrophysiological, molecular, and gene-knockout methods. Two channels, a large, Ca2+-activated K+ channel (BK) and a store-operated Ca2+ channel (SOCC), can be defined with respect to molecular structure and function. Human BK, comprised of a pore-forming α-subunit and an accessory β1-subunit, operate as Ca2+-sensing feedback modulators of contractile tone. SOCC have also been characterized in a mouse cell line; they are comprised of molecules belonging to the transient receptor potential subfamily.
AbstractProtein Arginine Methyltransferase (PRMT) 5 is the major type 2 methyltransferase catalyzing symmetric dimethylation (SDM) of arginine. PRMT5 inhibition or deletion in CD4 Th cells reduces TcR engagement-induced IL-2 production and Th cell expansion and confers protection against experimental autoimmune encephalomyelitis (EAE), the animal model of Multiple Sclerosis. However, the mechanisms by which PRMT5 modulates T helper (Th) cell proliferation are still not completely understood and neither are the methylation targets in T cells. In this manuscript, we uncover the role of PRMT5 on alternative splicing (AS) in activated T cells and identify several targets of PRMT5 SDM involved in splicing. In addition, we find a possible link between PRMT5 mediated AS of Trpm4 (Transient Receptor Potential Cation Channel Subfamily M Member 4) and TcR/NFAT signaling/IL-2 production. This understanding may guide development of drugs targeting these processes to benefit patients with T cell-mediated diseases.
Transient Receptor Potential Canonical 3 and Nuclear Factor of Activated T Cells C3 Signaling Pathway Critically Regulates Myocardial Fibrosis