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 Ludwig Krabben
A1 Anna Fassio
A1 Vikram Kjøller Bhatia
A1 Arndt Pechstein
A1 Franco Onofri
A1 Manuela Fadda
A1 Mirko Messa
A1 Yijian Rao
A1 Oleg Shupliakov
A1 Dimitrios Stamou
A1 Fabio Benfenati
A1 Volker Haucke
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.