TY - JOUR
T1 - Postsynaptic membrane addition depends on the discs-large-interacting t-SNARE Gtaxin
AU - Gorczyca, David
AU - Ashley, James
AU - Speese, Sean
AU - Gherbesi, Norberto
AU - Thomas, Ulrich
AU - Gundelfinger, Eckart
AU - Gramates, L. Sian
AU - Budnik, Vivian
PY - 2007/1/31
Y1 - 2007/1/31
N2 - Targeted membrane addition is a hallmark of many cellular functions. In the nervous system, modification of synaptic membrane size has a major impact on synaptic function. However, because of the complex shape of neurons and the need to target membrane addition to very small and polarized synaptic compartments, this process is poorly understood. Here, we show that Gtaxin (GTX), a Drosophilat-SNARE (target-soluble N-ethylmaleimide-sensitive factor attachment protein receptor), is required for expansion of postsynaptic membranes during new synapse formation. Mutations in gtx lead to drastic reductions in postsynaptic membrane surface, whereas gtx upregulation results in the formation of complex membrane structures at ectopic sites. Postsynaptic GTX activity depends on its direct interaction with Discs-Large (DLG), a multidomain scaffolding protein of the PSD-95(postsynaptic density protein-95) family with key roles in cell polarity and formation of cellular junctions as well as synaptic protein anchoring and trafficking. We show that DLG selectively determines the postsynaptic distribution of GTX to type I, but not to type II or type III boutons on the same cell, thereby defining sites of membrane addition to this unique set of glutamatergic synapses. We provide a mechanistic explanation for selective targeted membrane expansion at specific synaptic junctions.
AB - Targeted membrane addition is a hallmark of many cellular functions. In the nervous system, modification of synaptic membrane size has a major impact on synaptic function. However, because of the complex shape of neurons and the need to target membrane addition to very small and polarized synaptic compartments, this process is poorly understood. Here, we show that Gtaxin (GTX), a Drosophilat-SNARE (target-soluble N-ethylmaleimide-sensitive factor attachment protein receptor), is required for expansion of postsynaptic membranes during new synapse formation. Mutations in gtx lead to drastic reductions in postsynaptic membrane surface, whereas gtx upregulation results in the formation of complex membrane structures at ectopic sites. Postsynaptic GTX activity depends on its direct interaction with Discs-Large (DLG), a multidomain scaffolding protein of the PSD-95(postsynaptic density protein-95) family with key roles in cell polarity and formation of cellular junctions as well as synaptic protein anchoring and trafficking. We show that DLG selectively determines the postsynaptic distribution of GTX to type I, but not to type II or type III boutons on the same cell, thereby defining sites of membrane addition to this unique set of glutamatergic synapses. We provide a mechanistic explanation for selective targeted membrane expansion at specific synaptic junctions.
KW - Discs-large
KW - Drosophila
KW - MAGUK
KW - Membrane addition
KW - Neuromuscular junction
KW - Postsynaptic plasticity
UR - http://www.scopus.com/inward/record.url?scp=33846813482&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33846813482&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.3160-06.2007
DO - 10.1523/JNEUROSCI.3160-06.2007
M3 - Article
C2 - 17267557
AN - SCOPUS:33846813482
SN - 0270-6474
VL - 27
SP - 1033
EP - 1044
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 5
ER -