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J Neurosci. 2011 Dec 7;31(49):18149-54. doi: 10.1523/JNEUROSCI.4345-11.2011.

Synapsin I senses membrane curvature by an amphipathic lipid packing sensor motif.

Author information

1
Institute of Chemistry and Biochemistry and Neurocure Cluster of Excellence, Freie Universit├Ąt, 14195 Berlin, Germany.

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.

PMID:
22159126
DOI:
10.1523/JNEUROSCI.4345-11.2011
[Indexed for MEDLINE]
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