Biology subjects

Hou, P.

Publications and source records attributed to Hou, P..

2 recordsLinked to original sources

bioRxiv2019

The inverse relationship between fibronectin and neuroligins in the embryonic rat colon

Our previous study identified that the abnormal expression of fibronectin (FN), neuroligin-1 (NL1) and neuroligin-2 (NL2) in the colons of children with Hirschsprung disease (HSCR), but the correlated relationship between the three in the development of the enteric nervous system (ENS) remains unclear. Colons of Wistar rats and PC12 neurons were used to investigate the relationship between FN and the neuroligins (NLs). Colon tissues from thirty healthy embryonic rats, including fifteen at embryonic day 16 (E16), eight at E18, seven at E20, and fifteen newborn rats within 24 hours (Ep0) were analyzed to determine the correlated expression of FN and NLs using Western blot (WB) analysis and real-time fluorescence quantitative PCR (qRT-PCR) methods. Small interfering ribonucleic acid (siRNA) targeting and gene plasmids were used to explore the functional interaction between FN and NLs by using PC12 neuron cells. Furthermore, we used recombinant FN and NL proteins to confirm their interactions. Our studies showed that there were downregulatory effects between FN and the NLs in the embryonic rat colon and different cell lines, indicating that FN and NLs could directly regulate each other, and there is a negative linear correlation between them. The imbalanced interaction between extracellular matrix and synapse-related genes may provide a new perspective for the pathogenesis and treatment of HSCR and neuronal intestinal malformations (NIMs).

cell biology↗

bioRxiv2019

ML277 specifically enhances pore opening of KCNQ1 with VSD at the activated state by modulating VSD-pore coupling

In response to membrane depolarization, the KCNQ1 potassium channel opens at the intermediate (IO) and activated (AO) states that correspond to the stepwise activation of the voltage sensing domain (VSD) to the intermediate (I) and activated (A) states. In the heart, KCNQ1 associates with the auxiliary subunit KCNE1 to form the IKs channel that regulates heart rhythm. More than 300 of loss-of-function KCNQ1 mutations cause long QT syndrome (LQTS). KCNE1 suppresses the IO state so that the IKs channel opens only to the AO state. Thus, enhancing AO state presents a potential therapy for anti-LQTS. Here, we systematically tested modulations of KCNQ1 channels by a KCNQ1 activator, ML277. It enhances the current amplitude, slows down activation, deactivation and inactivation kinetics, shifts the voltage dependence of activation to more positive voltages, decreases the Rb+/K+ permeability ratio, and selectively increases currents of mutant KCNQ1 channels that open only to the AO state. All these observations are consistent with the mechanism that ML277 specifically potentiates the AO state. On the other hand, ML277 does not affect the VSD activation, suggesting that it potentiates the AO state by enhancing the electromechanical (E-M) coupling when the VSD moves to the activated state. Our results suggest that ML277 provides a unique tool to investigate the gating mechanism of KCNQ1 and IKs channels. The specificity of ML277 to increase the AO state of native IKs currents also suggests a new strategy for anti-LQTS therapy.

biophysics↗