The activation of Ca2+ entry through store-operated channels by agonists that deplete Ca2+ from the endoplasmic reticulum (ER) is a ubiquitous signaling mechanism, the molecular basis of which has remained elusive for...The activation of Ca2+ entry through store-operated channels by agonists that deplete Ca2+ from the endoplasmic reticulum (ER) is a ubiquitous signaling mechanism, the molecular basis of which has remained elusive for the past two decades. Store-operated Ca2+-release-activated Ca2+ (CRAC) channels constitute the sole pathway for Ca2+ entry following antigen-receptor engagement. In a set of breakthrough studies over the past two years, stromal interaction molecule 1 (STIM1, the ER Ca2+ sensor) and Orai1 (a pore-forming subunit of the CRAC channel) have been identified. Here we review these recent studies and the insights they provide into the mechanism of store-operated Ca2+ channels (SOCCs).展开更多
Neuroglial cells are homeostatic neural cells. Generally, they are electrically non-excitable and their activation is associated with the generation of complex intracellular Ca^2＋ signals that define the ＂Ca^2＋ exc...Neuroglial cells are homeostatic neural cells. Generally, they are electrically non-excitable and their activation is associated with the generation of complex intracellular Ca^2＋ signals that define the ＂Ca^2＋ excitability＂ of glia. In mammalian glial cells the major source of Ca^2＋ for this excitability is the lumen of the endoplasmic reticulum （ER）, which is ultimately （re）filled from the extracellular space. This occurs via store-operated Ca^2＋ entry （SOCE） which is supported by a specific signaling system connecting the ER with plasmalemmal Ca^2＋ entry. Here, emptying of the ER Ca^2＋ store is necessary and sufficient for the activation of SOCE, and without Ca^2＋ influx via SOCE the ER store cannot be refilled. The molecular arrangements underlying SOCE are relatively complex and include plasmalemmal channels, ER Ca^2＋ sensors, such as stromal interaction molecule, and possibly ER Ca^2＋ pumps （of the SERCA type）. There are at least two sets of plasmalemmal channels mediating SOCE, the Ca2＊-release activated channels, Orai, and transient receptor potential （TRP） channels. The molecular identity of neuroglial SOCE has not been yet identified unequivocally. However, it seems that Orai is predominantly expressed in microglia, whereas astrocytes and oligodendrocytes rely more on TRP channels to produce SOCE. In physiological conditions the SOCE pathway is instrumental for the sustained phase of the Ca^2＋ signal observed following stimulation of metabotropic receptors on glial cells.展开更多
Hepatitis B virus X（HBx） protein plays a pivotal role in the development of hepatitis B virus（HBV）-associated hepatocellular carcinoma.Although regulation of cytosolic calcium is essential for HBV replication and ...Hepatitis B virus X（HBx） protein plays a pivotal role in the development of hepatitis B virus（HBV）-associated hepatocellular carcinoma.Although regulation of cytosolic calcium is essential for HBV replication and is mediated by HBx protein,the mechanism of HBx protein regulating intracellular calcium level remains poorly understood.The present study examined whether HBx protein elevated the intracellular calcium through interacting with storeoperated calcium entry（SOCE） components,Orai1 and stromal interaction molecule 1,and then identified the targets of HBx protein,with an attempt to understand the mechanism of HBx protein upsetting intracellular calcium homeostasis.By employing co-immunoprecipitation and GST-pull-down assay,we found that Orai1 protein interacted with HBx protein,and the C-terminus of Orai1 was implicated in the interaction.Confocal microscopy also revealed that HBx protein could co-localize with full-length Orai1 protein in HEK293 cells.Moreover,live cell calcium imaging exhibited that HBx protein elevated intracellular calcium,possibly by binding to SOCE components.Our results suggest that HBx protein binds to STIM1-Orai1 complexes to positively regulate the activity of plasma membrane store-operated calcium channels.展开更多
文摘The activation of Ca2+ entry through store-operated channels by agonists that deplete Ca2+ from the endoplasmic reticulum (ER) is a ubiquitous signaling mechanism, the molecular basis of which has remained elusive for the past two decades. Store-operated Ca2+-release-activated Ca2+ (CRAC) channels constitute the sole pathway for Ca2+ entry following antigen-receptor engagement. In a set of breakthrough studies over the past two years, stromal interaction molecule 1 (STIM1, the ER Ca2+ sensor) and Orai1 (a pore-forming subunit of the CRAC channel) have been identified. Here we review these recent studies and the insights they provide into the mechanism of store-operated Ca2+ channels (SOCCs).
基金supported by an Alzheimer’s Research Trust(UK)Programme Grant(ART/PG2004A/1)to A.V.by a National Science Foundation grant(CBET 0943343)to V.P
文摘Neuroglial cells are homeostatic neural cells. Generally, they are electrically non-excitable and their activation is associated with the generation of complex intracellular Ca^2＋ signals that define the ＂Ca^2＋ excitability＂ of glia. In mammalian glial cells the major source of Ca^2＋ for this excitability is the lumen of the endoplasmic reticulum （ER）, which is ultimately （re）filled from the extracellular space. This occurs via store-operated Ca^2＋ entry （SOCE） which is supported by a specific signaling system connecting the ER with plasmalemmal Ca^2＋ entry. Here, emptying of the ER Ca^2＋ store is necessary and sufficient for the activation of SOCE, and without Ca^2＋ influx via SOCE the ER store cannot be refilled. The molecular arrangements underlying SOCE are relatively complex and include plasmalemmal channels, ER Ca^2＋ sensors, such as stromal interaction molecule, and possibly ER Ca^2＋ pumps （of the SERCA type）. There are at least two sets of plasmalemmal channels mediating SOCE, the Ca2＊-release activated channels, Orai, and transient receptor potential （TRP） channels. The molecular identity of neuroglial SOCE has not been yet identified unequivocally. However, it seems that Orai is predominantly expressed in microglia, whereas astrocytes and oligodendrocytes rely more on TRP channels to produce SOCE. In physiological conditions the SOCE pathway is instrumental for the sustained phase of the Ca^2＋ signal observed following stimulation of metabotropic receptors on glial cells.
基金supported by grants from the National Natural Science Foundation of China(No.81001063)the Fundamental Research Funds for the Central Universities(No.2015QN150)
文摘Hepatitis B virus X（HBx） protein plays a pivotal role in the development of hepatitis B virus（HBV）-associated hepatocellular carcinoma.Although regulation of cytosolic calcium is essential for HBV replication and is mediated by HBx protein,the mechanism of HBx protein regulating intracellular calcium level remains poorly understood.The present study examined whether HBx protein elevated the intracellular calcium through interacting with storeoperated calcium entry（SOCE） components,Orai1 and stromal interaction molecule 1,and then identified the targets of HBx protein,with an attempt to understand the mechanism of HBx protein upsetting intracellular calcium homeostasis.By employing co-immunoprecipitation and GST-pull-down assay,we found that Orai1 protein interacted with HBx protein,and the C-terminus of Orai1 was implicated in the interaction.Confocal microscopy also revealed that HBx protein could co-localize with full-length Orai1 protein in HEK293 cells.Moreover,live cell calcium imaging exhibited that HBx protein elevated intracellular calcium,possibly by binding to SOCE components.Our results suggest that HBx protein binds to STIM1-Orai1 complexes to positively regulate the activity of plasma membrane store-operated calcium channels.
