Cell migration requires the generation of branched actin networks and recruitment of vesicular membrane that power the protrusion of the plasma membrane in lamellipodia.However,the molecular mechanisms underlying dyna...Cell migration requires the generation of branched actin networks and recruitment of vesicular membrane that power the protrusion of the plasma membrane in lamellipodia.However,the molecular mechanisms underlying dynamic recruitment of vesicular membrane during cell migration remain elusive.Here,we report a critical mechanism underlying epidermal growth factor(EGF)-elicited Akt signaling-steered cell migration.Using functional proteomics screen,we identified a novel ADP-ribosylation factor 6(ARF6)–ACAP4 signaling regulator,Acapin,which inhibits the GTPase-activating protein(GAP)activity of ACAP4 to activate ARF6 GTPase in vitro.In cells,EGF stimulation elicits Akt signaling,which recruits Acapin to the lamellipodium membrane via phosphorylation of Acapin at its Ser247 residue and enhances the binding of Acapin to ACAP4 to elevate the ARF6-GTP level.Therefore,Acapin is required for efficiently stimulating cell migration by EGF–Akt signaling.Together,our results demonstrate the role of Acapin in relaying the Akt signaling cascade during cell migration processes.展开更多
基金supported by grants from the Ministry of Science and Technology of China and the National Natural Science Foundationof China(2022YFA1303100,32090040,92254302,91953000,32300649,32400593,32170737,31501130,91854203,31621002,and 2017YFA0503600)the Ministry of Education(IRT_17R102)+1 种基金the Fundamental Research Funds for the Central Universities(KB910000oo07,KB9100000006,and KB9100000013)Plans for Major Provincial Science&Technology Projects of Anhui Province(202303a0702003).
文摘Cell migration requires the generation of branched actin networks and recruitment of vesicular membrane that power the protrusion of the plasma membrane in lamellipodia.However,the molecular mechanisms underlying dynamic recruitment of vesicular membrane during cell migration remain elusive.Here,we report a critical mechanism underlying epidermal growth factor(EGF)-elicited Akt signaling-steered cell migration.Using functional proteomics screen,we identified a novel ADP-ribosylation factor 6(ARF6)–ACAP4 signaling regulator,Acapin,which inhibits the GTPase-activating protein(GAP)activity of ACAP4 to activate ARF6 GTPase in vitro.In cells,EGF stimulation elicits Akt signaling,which recruits Acapin to the lamellipodium membrane via phosphorylation of Acapin at its Ser247 residue and enhances the binding of Acapin to ACAP4 to elevate the ARF6-GTP level.Therefore,Acapin is required for efficiently stimulating cell migration by EGF–Akt signaling.Together,our results demonstrate the role of Acapin in relaying the Akt signaling cascade during cell migration processes.
