RT Journal Article SR Electronic T1 Synapsin I Senses Membrane Curvature by an Amphipathic Lipid Packing Sensor Motif JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 18149 OP 18154 DO 10.1523/JNEUROSCI.4345-11.2011 VO 31 IS 49 A1 Krabben, Ludwig A1 Fassio, Anna A1 Bhatia, Vikram Kjøller A1 Pechstein, Arndt A1 Onofri, Franco A1 Fadda, Manuela A1 Messa, Mirko A1 Rao, Yijian A1 Shupliakov, Oleg A1 Stamou, Dimitrios A1 Benfenati, Fabio A1 Haucke, Volker YR 2011 UL http://www.jneurosci.org/content/31/49/18149.abstract AB 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.