Large-conductance Ca^(2+)-activated K+channels(BK channels)constitute an key physiological link between cellular Ca^(2+) signaling and electrical signaling at the plasma membrane.Thus these channels are critical to th...Large-conductance Ca^(2+)-activated K+channels(BK channels)constitute an key physiological link between cellular Ca^(2+) signaling and electrical signaling at the plasma membrane.Thus these channels are critical to the control of action potential firing and neurotrans-mitter release in several types of neurons,as well as the dynamic control of smooth muscle tone in resis-tance arteries,airway,and bladder.Recent advances in our understanding of K^(+) channel structure and function have led to new insight toward the molecular mecha-nisms of opening and closing(gating)of these chan-nels.Here we will focus on mechanisms of BK channel gating by Ca^(2+),transmembrane voltage,and auxiliary subunit proteins.展开更多
As evolutionarily conserved signals,roof plate-specific spondins(R-spondins;RSPOs)are a family with four members(RSPO1e4)exerting distinctly different functions.RSPOs have five receptors and correlate with different s...As evolutionarily conserved signals,roof plate-specific spondins(R-spondins;RSPOs)are a family with four members(RSPO1e4)exerting distinctly different functions.RSPOs have five receptors and correlate with different signaling pathways through these receptors and then perform various functions.Moreover,their best-known molecular function is the capacity to enhance WNT signaling pathways,which play critical roles in several processes.A recent study shows that RSPOs not only potentiate the WNT/beta(b)-catenin signaling pathway but are also involved in the WNT/planar cell polarity signaling pathway.RSPOs influence liver homeostasis and the development of multiple liver diseases.RSPO1 increases cell proliferation,protects hepatocytes from injury,improves liver regenerative potential,and affects liver metabolic zonation.RSPO2 not only regulates proliferation-associated genes and promotes differentiation in the liver but also participates in liver fibrosis through the WNT/b-catenin signaling pathway.RSPO3 is a key determinant of proper liver function,such as promoting hepatocyte regeneration and maintaining liver zonation.RSPO3 is upregulated in liver fibrosis and livers of patients with nonalcoholic steatohepatitis.Besides,RSPO2 and RSPO3 are confirmed as oncogenes and involved in the occurrence of liver cancer.The role of RSPO4 in the liver remains unclear.In this review,the structural and biochemical properties of RSPOs and their receptors and their roles in liver homeostasis and disease are summarized.展开更多
基金supported in part by the National Institute of General Medical Science of the National Institutes of Health(Grant No.R01GM068523).
文摘Large-conductance Ca^(2+)-activated K+channels(BK channels)constitute an key physiological link between cellular Ca^(2+) signaling and electrical signaling at the plasma membrane.Thus these channels are critical to the control of action potential firing and neurotrans-mitter release in several types of neurons,as well as the dynamic control of smooth muscle tone in resis-tance arteries,airway,and bladder.Recent advances in our understanding of K^(+) channel structure and function have led to new insight toward the molecular mecha-nisms of opening and closing(gating)of these chan-nels.Here we will focus on mechanisms of BK channel gating by Ca^(2+),transmembrane voltage,and auxiliary subunit proteins.
基金This work was supported by grants from the Scientific Research Common Program of Beijing Municipal Commission of Education(No.KM202010025029)the National Natural Science Foundation of China(No.82070623 and 81970532)the Beijing Natural Science Foundation(No.7202007).
文摘As evolutionarily conserved signals,roof plate-specific spondins(R-spondins;RSPOs)are a family with four members(RSPO1e4)exerting distinctly different functions.RSPOs have five receptors and correlate with different signaling pathways through these receptors and then perform various functions.Moreover,their best-known molecular function is the capacity to enhance WNT signaling pathways,which play critical roles in several processes.A recent study shows that RSPOs not only potentiate the WNT/beta(b)-catenin signaling pathway but are also involved in the WNT/planar cell polarity signaling pathway.RSPOs influence liver homeostasis and the development of multiple liver diseases.RSPO1 increases cell proliferation,protects hepatocytes from injury,improves liver regenerative potential,and affects liver metabolic zonation.RSPO2 not only regulates proliferation-associated genes and promotes differentiation in the liver but also participates in liver fibrosis through the WNT/b-catenin signaling pathway.RSPO3 is a key determinant of proper liver function,such as promoting hepatocyte regeneration and maintaining liver zonation.RSPO3 is upregulated in liver fibrosis and livers of patients with nonalcoholic steatohepatitis.Besides,RSPO2 and RSPO3 are confirmed as oncogenes and involved in the occurrence of liver cancer.The role of RSPO4 in the liver remains unclear.In this review,the structural and biochemical properties of RSPOs and their receptors and their roles in liver homeostasis and disease are summarized.
