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
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.
