Dear Editor,Rab7A(Ras-related protein Rab-7a),a member of the Rab family of small GTPases,has been demonstrated to be a crucial regulator of mammalian autophagic and endosomal pathways(Gutierrez et al.,2004;Yamano et ...Dear Editor,Rab7A(Ras-related protein Rab-7a),a member of the Rab family of small GTPases,has been demonstrated to be a crucial regulator of mammalian autophagic and endosomal pathways(Gutierrez et al.,2004;Yamano et al.,2018).During mammalian autophagy,Rab7A can facilitate the maturation of autophagosomes and their fusion with lysosomes through its interactions with relevant regulatory proteins and binding partners(Chua et al.,2011;Gutierrez et al.,2004;Stroupe,2018;Vaites et al.,2018).Particularly,the GDP(guanosine-5'-diphosphate)-bound inactive Rab7A is reported to be recruited to autophagosomes by its GEF(guanine nucleotide exchange factor)protein,the MON1/CCZ1/C18orf8 complex(Fig.1A),which can specifically convert Rab7A to its GTP(guanosine-5'-triphosphate)-bound active state(Nordmann et al.,2010).The precise spatiotemporal regulation of the activity of Rab7A is critical for proper autophagic flux in mammals.Recently,two Cryo-EM(cryo-electron microscopy)structures of the Mon1/Ccz1/Bulli complex from Drosophila were reported(Herrmann et al.,2023;Yong et al.,2023).However,due to the lack of complex structures,how the mammalian MON1(monensin sensitivity 1)/CCZ1(calcium caffeine zinc sensitivity 1)/C18orf8(chromosome 18 open reading frame 8)complex specifically recognizes the GDP-bound inactive Rab7A and achieves its specific GEF activity for Rab7A remains unclear.展开更多
Autophagy is a highly conserved cellular program in eukaryotic cells which mediates the degradation of cytoplasmic components through the lysosome,also named the vacuole in plants.However,the molecular mechanisms unde...Autophagy is a highly conserved cellular program in eukaryotic cells which mediates the degradation of cytoplasmic components through the lysosome,also named the vacuole in plants.However,the molecular mechanisms underlying the fusion of autophagosomes with the vacuole remain unclear.Here,we report the functional characterization of a rice(Oryza sativa)mutant with defects in storage protein transport in endosperm cells and accumulation of numerous autophagosomes in root cells.Cytological and immunocytochemical experiments showed that this mutant exhibits a defect in the fusion between autophagosomes and vacuoles.The mutant harbors a loss-of-function mutation in the rice homolog of Arabidopsis thaliana MONENSIN SENSITIVITY1(MON1).Biochemical and genetic evidence revealed a synergistic interaction between rice MON1 and AUTOPHAGY-RELATED 8a in maintaining normal growth and development.In addition,the rice mon1 mutant disrupted storage protein sorting to protein storage vacuoles.Furthermore,quantitative proteomics verified that the loss of MON1 function influenced diverse biological pathways including autophagy and vacuolar transport,thus decreasing the transport of autophagic and vacuolar cargoes to vacuoles.Together,our findings establish a molecular link between autophagy and vacuolar protein transport,and offer insights into the dual functions of the MON1–CCZ1(CAFFEINE ZINC SENSITIVITY1)complex in plants.展开更多
基金supported by grants from the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB1060000)the National Basic Research Program of China(2022YFC2303102)+4 种基金the National Natural Science Foundation of China(92253301,32071219,21822705)the CAS Youth Interdisciplinary Team(JCTD-2022-10)(to L.P.)the STI2030-Major Project(2022ZD0207400)(to Y.Z.)the Shanghai Key Laboratory of Aging Studies(19DZ2260400)(to Y.Z.)the Basic Research Pioneer Project by the Science and Technology Commission of Shanghai Municipality(STCSM).
文摘Dear Editor,Rab7A(Ras-related protein Rab-7a),a member of the Rab family of small GTPases,has been demonstrated to be a crucial regulator of mammalian autophagic and endosomal pathways(Gutierrez et al.,2004;Yamano et al.,2018).During mammalian autophagy,Rab7A can facilitate the maturation of autophagosomes and their fusion with lysosomes through its interactions with relevant regulatory proteins and binding partners(Chua et al.,2011;Gutierrez et al.,2004;Stroupe,2018;Vaites et al.,2018).Particularly,the GDP(guanosine-5'-diphosphate)-bound inactive Rab7A is reported to be recruited to autophagosomes by its GEF(guanine nucleotide exchange factor)protein,the MON1/CCZ1/C18orf8 complex(Fig.1A),which can specifically convert Rab7A to its GTP(guanosine-5'-triphosphate)-bound active state(Nordmann et al.,2010).The precise spatiotemporal regulation of the activity of Rab7A is critical for proper autophagic flux in mammals.Recently,two Cryo-EM(cryo-electron microscopy)structures of the Mon1/Ccz1/Bulli complex from Drosophila were reported(Herrmann et al.,2023;Yong et al.,2023).However,due to the lack of complex structures,how the mammalian MON1(monensin sensitivity 1)/CCZ1(calcium caffeine zinc sensitivity 1)/C18orf8(chromosome 18 open reading frame 8)complex specifically recognizes the GDP-bound inactive Rab7A and achieves its specific GEF activity for Rab7A remains unclear.
基金supported by grants from the National Key R&D Program of China(2021YFF1000200)Innovation Program of Chinese Academy of Agricultural Sciences,International Science&Technology Innovation Program of Chinese Academy of Agricultural Sciences(CAAS-ZDRW202109)+2 种基金National Natural Science Foundation of China(31830064 and 32172085)supported by the Central Public-Interest Scientific Institution Basal Research Fund,China(Y2021YJ18)Jiangsu Nanjing Rice Germplasm Resources National Field Observation and Research Station。
文摘Autophagy is a highly conserved cellular program in eukaryotic cells which mediates the degradation of cytoplasmic components through the lysosome,also named the vacuole in plants.However,the molecular mechanisms underlying the fusion of autophagosomes with the vacuole remain unclear.Here,we report the functional characterization of a rice(Oryza sativa)mutant with defects in storage protein transport in endosperm cells and accumulation of numerous autophagosomes in root cells.Cytological and immunocytochemical experiments showed that this mutant exhibits a defect in the fusion between autophagosomes and vacuoles.The mutant harbors a loss-of-function mutation in the rice homolog of Arabidopsis thaliana MONENSIN SENSITIVITY1(MON1).Biochemical and genetic evidence revealed a synergistic interaction between rice MON1 and AUTOPHAGY-RELATED 8a in maintaining normal growth and development.In addition,the rice mon1 mutant disrupted storage protein sorting to protein storage vacuoles.Furthermore,quantitative proteomics verified that the loss of MON1 function influenced diverse biological pathways including autophagy and vacuolar transport,thus decreasing the transport of autophagic and vacuolar cargoes to vacuoles.Together,our findings establish a molecular link between autophagy and vacuolar protein transport,and offer insights into the dual functions of the MON1–CCZ1(CAFFEINE ZINC SENSITIVITY1)complex in plants.
