PT  - JOURNAL ARTICLE
AU  - Ludwig Krabben
AU  - Anna Fassio
AU  - Vikram Kjøller Bhatia
AU  - Arndt Pechstein
AU  - Franco Onofri
AU  - Manuela Fadda
AU  - Mirko Messa
AU  - Yijian Rao
AU  - Oleg Shupliakov
AU  - Dimitrios Stamou
AU  - Fabio Benfenati
AU  - Volker Haucke
TI  - Synapsin I Senses Membrane Curvature by an Amphipathic Lipid Packing Sensor Motif
AID  - 10.1523/JNEUROSCI.4345-11.2011
DP  - 2011 Dec 07
TA  - The Journal of Neuroscience
PG  - 18149--18154
VI  - 31
IP  - 49
4099  - http://www.jneurosci.org/content/31/49/18149.short
4100  - http://www.jneurosci.org/content/31/49/18149.full
SO  - J. Neurosci.2011 Dec 07; 31
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.