Mobilization of intracellular Ca2+ stores is involved inmany diverse cell functions, including: cell proliferation;differentiation; fertilization; muscle contraction; secre-tion of neurotransmitters, hormones and enzy...Mobilization of intracellular Ca2+ stores is involved inmany diverse cell functions, including: cell proliferation;differentiation; fertilization; muscle contraction; secre-tion of neurotransmitters, hormones and enzymes;and lymphocyte activation and proliferation. Cyclic ad-enosine diphosphate ribose(cADPR) is an endogenousCa2+ mobilizing nucleotide present in many cell typesand species, from plants to animals. cADPR is formedby ADP-ribosyl cyclases from nicotinamide adenine di-nucleotide. The main ADP-ribosyl cyclase in mammalsis CD38, a multi-functional enzyme and a type Ⅱ mem-brane protein. It has been shown that many extracel-lular stimuli can induce cADPR production that leadsto calcium release or influx, establishing cADPR as asecond messenger. cADPR has been linked to a widevariety of cellular processes, but the molecular mecha-nisms regarding cADPR signaling remain elusive. Theaim of this review is to summarize the CD38/cADPR/Ca2+ signaling pathway, focusing on the recent advanc-es involving the mechanism and physiological functionsof cADPR-mediated Ca2+ mobilization.展开更多
Transient receptor potential canonical subfamily member 3(TRPC3) is known to be important for neural development and the formation of neuronal networks. Here, we investigated the role of TRPC3 in undifferentiated mous...Transient receptor potential canonical subfamily member 3(TRPC3) is known to be important for neural development and the formation of neuronal networks. Here, we investigated the role of TRPC3 in undifferentiated mouse embryonic stem cells(mESCs) and during the differentiation of mESCs into neurons. CRISPR/Cas9-mediated knockout(KO) of TRPC3 induced apoptosis and the disruption of mitochondrial membrane potential both in undifferentiated mESCs and in those undergoing neural differentiation. In addition, TRPC3 KO impaired the pluripotency of mESCs. TRPC3 KO also dramatically repressed the neural differentiation of mESCs by inhibiting the expression of markers for neural progenitors, neurons, astrocytes and oligodendrocytes.Taken together, our new data demonstrate an important function of TRPC3 with regards to the survival, pluripotency and neural differentiation of mESCs.展开更多
Dear Editor,Middle East respiratory syndrome-related coronavirus(MERS-CoV)is the pathogen responsible for the outbreak of MERS,and we are currently being affected by coronavirus disease 2019(COVID-19)due to infection ...Dear Editor,Middle East respiratory syndrome-related coronavirus(MERS-CoV)is the pathogen responsible for the outbreak of MERS,and we are currently being affected by coronavirus disease 2019(COVID-19)due to infection by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).The S protein of SARS-CoV-2 or MERS-CoV binds angiotensin-converting enzyme 2(ACE2)or dipeptidyl peptidase-4(DPP4),respectively,to facilitate viral particles entry into cells1.The COVID-19 pandemic has caused major socioeconomic disruptions globally.展开更多
The dysregulation of autophagy,an evolutionarily conserved lysosomal degradation process,has been implicated in a wide variety of human diseases,and thus,small chemicals that modulate autophagy have therapeutic potent...The dysregulation of autophagy,an evolutionarily conserved lysosomal degradation process,has been implicated in a wide variety of human diseases,and thus,small chemicals that modulate autophagy have therapeutic potential.Here,we assessed the ability of active components isolated from Bupleurum falcatum,a popular Chinese herb,to modulate autophagy.We found that saikosaponin D(SsD)and A(SsA)but not C(SsC)potently and reversibly inhibited the fusion of autophagosomes and lysosomes,resulting in the accumulation of autophagosomes,an increased lysosomal pH,and TFEB nuclear translocation.RAB5A knockdown or the expression of a dominant-negative RAB5 mutant significantly reduced the ability of SsD or SsA to block autophagy.Enterovirus A71(EV-A71),the cause of hand-foot-mouth disease,has been shown to induce autophagy.We found that SsD potently inhibited EV-A71 RNA replication and subsequent viral protein synthesis,thereby preventing EV-A71-induced cell death.ATG5 knockdown inhibited EV-A71 viral protein synthesis,whereas autophagy induction by rapamycin promoted synthesis.Taken together,our data indicate that SsD and SsA are potent late-stage autophagy inhibitors that can be used to prevent EV-A71 infection.展开更多
基金Supported by Research Grant Council grants,No.782709M,No.785911M,No.769912M and No.785213M
文摘Mobilization of intracellular Ca2+ stores is involved inmany diverse cell functions, including: cell proliferation;differentiation; fertilization; muscle contraction; secre-tion of neurotransmitters, hormones and enzymes;and lymphocyte activation and proliferation. Cyclic ad-enosine diphosphate ribose(cADPR) is an endogenousCa2+ mobilizing nucleotide present in many cell typesand species, from plants to animals. cADPR is formedby ADP-ribosyl cyclases from nicotinamide adenine di-nucleotide. The main ADP-ribosyl cyclase in mammalsis CD38, a multi-functional enzyme and a type Ⅱ mem-brane protein. It has been shown that many extracel-lular stimuli can induce cADPR production that leadsto calcium release or influx, establishing cADPR as asecond messenger. cADPR has been linked to a widevariety of cellular processes, but the molecular mecha-nisms regarding cADPR signaling remain elusive. Theaim of this review is to summarize the CD38/cADPR/Ca2+ signaling pathway, focusing on the recent advanc-es involving the mechanism and physiological functionsof cADPR-mediated Ca2+ mobilization.
基金supported by the Hong Kong Research Grants Council(RGC)General Research Fund awards(662113,16101714,16100115)the ANR/RGC joint research scheme award(AHKUST601/13)+1 种基金the Hong Kong Theme-based Research Scheme award(T13-706/11-1)the Hong Kong Innovation and Technology Commission(ITCPD/17-9)
文摘Transient receptor potential canonical subfamily member 3(TRPC3) is known to be important for neural development and the formation of neuronal networks. Here, we investigated the role of TRPC3 in undifferentiated mouse embryonic stem cells(mESCs) and during the differentiation of mESCs into neurons. CRISPR/Cas9-mediated knockout(KO) of TRPC3 induced apoptosis and the disruption of mitochondrial membrane potential both in undifferentiated mESCs and in those undergoing neural differentiation. In addition, TRPC3 KO impaired the pluripotency of mESCs. TRPC3 KO also dramatically repressed the neural differentiation of mESCs by inhibiting the expression of markers for neural progenitors, neurons, astrocytes and oligodendrocytes.Taken together, our new data demonstrate an important function of TRPC3 with regards to the survival, pluripotency and neural differentiation of mESCs.
基金This work was supported by Hong Kong Research Grant Council(RGC)grants(11101717 and 11103620),NSFC(21778045 and 32070702)Shenzhen government research grant(JSGG20200225150702770).
文摘Dear Editor,Middle East respiratory syndrome-related coronavirus(MERS-CoV)is the pathogen responsible for the outbreak of MERS,and we are currently being affected by coronavirus disease 2019(COVID-19)due to infection by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).The S protein of SARS-CoV-2 or MERS-CoV binds angiotensin-converting enzyme 2(ACE2)or dipeptidyl peptidase-4(DPP4),respectively,to facilitate viral particles entry into cells1.The COVID-19 pandemic has caused major socioeconomic disruptions globally.
基金This work was supported by Hong Kong Research Grant Council(RGC)grants(785213,17126614,and 11101717),NSFC(21778045)the CAS-Croucher Funding Scheme,the Guangdong-Hong Kong joint innovation Research Scheme(2016A050503010)+1 种基金a Shenzhen government research grant(JCYJ20160229165235739 and JCYJ20170413141331470)to J.Y.it was partly supported by GRF(14105214)and NSFC(81671995,81471964)grants to M.L.H.
文摘The dysregulation of autophagy,an evolutionarily conserved lysosomal degradation process,has been implicated in a wide variety of human diseases,and thus,small chemicals that modulate autophagy have therapeutic potential.Here,we assessed the ability of active components isolated from Bupleurum falcatum,a popular Chinese herb,to modulate autophagy.We found that saikosaponin D(SsD)and A(SsA)but not C(SsC)potently and reversibly inhibited the fusion of autophagosomes and lysosomes,resulting in the accumulation of autophagosomes,an increased lysosomal pH,and TFEB nuclear translocation.RAB5A knockdown or the expression of a dominant-negative RAB5 mutant significantly reduced the ability of SsD or SsA to block autophagy.Enterovirus A71(EV-A71),the cause of hand-foot-mouth disease,has been shown to induce autophagy.We found that SsD potently inhibited EV-A71 RNA replication and subsequent viral protein synthesis,thereby preventing EV-A71-induced cell death.ATG5 knockdown inhibited EV-A71 viral protein synthesis,whereas autophagy induction by rapamycin promoted synthesis.Taken together,our data indicate that SsD and SsA are potent late-stage autophagy inhibitors that can be used to prevent EV-A71 infection.