title: Synapsin I senses membrane curvature by an amphipathic lipid packing sensor motif.
abstract: Sustained neurotransmitter release at synapses during high-frequency synaptic activity involves the mobilization of synaptic vesicles (SVs) from the tightly clustered reserve pool (RP). Synapsin I (Syn I), a brain-specific peripheral membrane protein that undergoes activity-dependent cycles of SV association and dissociation, is implicated in RP organization via its ability to cluster SVs. Although Syn I has affinity for phospholipids, the mechanism for the reversible association of synapsin with SV membranes remains enigmatic. Here, we show that rat Syn I is able to sense membrane curvature via an evolutionary conserved amphipathic lipid packing sensor motif (ALPS). Deletion or mutational inactivation of the ALPS impairs the ability of Syn I to associate with highly curved membranes and with SVs. Furthermore, a Syn I mutant lacking ALPS displays defects in its ability to undergo activity-induced cycles of dispersion and reclustering in neurons and fails to induce vesicle clustering in vitro. Our data suggest a crucial role for ALPS-mediated sensing of membrane curvature in regulating synapsin function.
authors.affiliation: Institute of Chemistry and Biochemistry and Neurocure Cluster of Excellence, Freie Universität, 14195 Berlin, Germany.
authors.forename: Ludwig
authors.initials: L
authors.lastname: Krabben
authors.forename: Anna
authors.initials: A
authors.lastname: Fassio
authors.forename: Vikram Kjøller
authors.initials: VK
authors.lastname: Bhatia
authors.forename: Arndt
authors.initials: A
authors.lastname: Pechstein
authors.forename: Franco
authors.initials: F
authors.lastname: Onofri
authors.forename: Manuela
authors.initials: M
authors.lastname: Fadda
authors.forename: Mirko
authors.initials: M
authors.lastname: Messa
authors.forename: Yijian
authors.initials: Y
authors.lastname: Rao
authors.forename: Oleg
authors.initials: O
authors.lastname: Shupliakov
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Stamou
authors.forename: Fabio
authors.initials: F
authors.lastname: Benfenati
authors.forename: Volker
authors.initials: V
authors.lastname: Haucke
mesh_terms: D000818:Animals; D002461:Cell Line, Transformed; D004622:Embryo, Mammalian; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes / Q000378:metabolism*; D008297:Male; D008567:Membranes, Artificial; D051379:Mice; D009474:Neurons / Q000166:cytology*; D017434:Protein Structure, Tertiary / Q000235:genetics; D016704:Synapsins / Q000235:genetics / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000235:genetics / Q000378:metabolism*; D014162:Transfection / Q000379:methods
chemical_list: D008055:Lipids; D008081:Liposomes; D008567:Membranes, Artificial; D016704:Synapsins; D049452:Green Fluorescent Proteins