RESUMO
Inwardly rectifying potassium (Kir) channels are widely distributed in many tissues and play important roles in physiological processes such as maintaining K+ homeostasis, regulating cell excitability and insulin secretion. The activity of Kir channels is regulated by a number of modulators,such as K+, Mg2+, pH, ATP, GPCR, PIP2, PKA, PKC, AA (arachidonic acid), etc. Study of the regulating mechanisms of Kir channel is a key step in understanding the physiology and physiopathology of these channels. Because many extra molecular signals regulate Kir channels via PKC pathway, much effort has been made over the past decade to understand role of PKC in regulating Kir channels. This paper summarizes the molecular basis of PKC modulation of Kir channels and the recent progression on the area.
RESUMO
Transient receptor potential(TRP) superfamily includes seven subfamilies and TRP channels are regulated by a wide variety of physical and chemical factors. Recently, several members of the TRP channel family have been reported to be regulated by phosphatidylinositol 4,5-bisphosphate(PIP2). The regulation is complex and it can be activation or inhibition, involving multiple mechanisms and factors. This review summarizes the PIP2 regulation of several TRP channels of different superfamilies and the related pathophysiological significance.
RESUMO
Phosphoinositide-specific phospholipase C-gamma1 (PLC-gamma1) has two pleckstrin homology (PH) domains: an amino-terminal domain (PH1) and a split PH domain (PH2). Here, we show that overlay assay of bovine brain tubulin pool with glutathione-S-transferase (GST)-PLC-gamma1 PH domain fusion proteins, followed by matrix-assisted laser-desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), identified 68-kDa neurofilament light chain (NF-L) as a binding protein of amino-terminal PH domain of PLC-gamma1. NF-L is known as a component of neuronal intermediate filaments, which are responsible for supporting the structure of myelinated axons in neuron. PLC-gamma1 and NF-L colocalized in the neurite in PC12 cells upon nerve growth factor stimulation. In vitro binding assay and immunoprecipitation analysis also showed a specific interaction of both proteins in differentiated PC12 cells. The phosphatidylinositol 4, 5-bisphosphate [PI(4,5)P2] hydrolyzing activity of PLC-gamma1 was slightly decreased in the presence of purified NF-L in vitro, suggesting that NF-L inhibits PLC-gamma1. Our results suggest that PLC-gamma1-associated NF-L sequesters the phospholipid from the PH domain of PLC-gamma1.