Research output: Contribution to journal › Article › peer-review
Synapsin I senses membrane curvature by an amphipathic lipid packing sensor motif. / Krabben, Ludwig; Fassio, Anna; Bhatia, Vikram Kjoller; Pechstein, Arndt; Onofri, Franco; Fadda, Manuela; Messa, Mirko; Rao, Yijian; Shupliakov, Oleg; Stamou, Dimitrios; Benfenati, Fabio; Haucke, Volker.
In: Journal of Neuroscience, Vol. 31, No. 49, 07.12.2011, p. 18149-18154.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Synapsin I senses membrane curvature by an amphipathic lipid packing sensor motif
AU - Krabben, Ludwig
AU - Fassio, Anna
AU - Bhatia, Vikram Kjoller
AU - Pechstein, Arndt
AU - Onofri, Franco
AU - Fadda, Manuela
AU - Messa, Mirko
AU - Rao, Yijian
AU - Shupliakov, Oleg
AU - Stamou, Dimitrios
AU - Benfenati, Fabio
AU - Haucke, Volker
PY - 2011/12/7
Y1 - 2011/12/7
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=83055171566&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.4345-11.2011
DO - 10.1523/JNEUROSCI.4345-11.2011
M3 - Article
C2 - 22159126
AN - SCOPUS:83055171566
VL - 31
SP - 18149
EP - 18154
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 49
ER -
ID: 40828886