Abstract
Synaptic cell adhesion molecules, including the neurexin ligands, neuroligins (NLs) and leucine-rich repeat transmembrane proteins (LRRTMs), are thought to organize synapse assembly and specify synapse function. To test the synaptic role of these molecules in vivo, we performed lentivirally mediated knockdown of NL3, LRRTM1, and LRRTM2 in CA1 pyramidal cells of WT and NL1 KO mice at postnatal day (P)0 (when synapses are forming) and P21 (when synapses are largely mature). P0 knockdown of NL3 in WT or NL1 KO neurons did not affect excitatory synaptic transmission, whereas P0 knockdown of LRRTM1 and LRRTM2 selectively reduced AMPA receptor-mediated synaptic currents. P0 triple knockdown of NL3 and both LRRTMs in NL1 KO mice yielded greater reductions in AMPA and NMDA receptor-mediated currents, suggesting functional redundancy between NLs and LRRTMs during early synapse development. In contrast, P21 knockdown of LRRTMs did not alter excitatory transmission, whereas NL manipulations supported a role for NL1 in maintaining NMDA receptor-mediated transmission. These results show that neurexin ligands in vivo form a dynamic synaptic cell adhesion network, with compensation between NLs and LRRTMs during early synapse development and functional divergence upon synapse maturation.
Bibliography
Soler-Llavina, G. J., Fuccillo, M. V., Ko, J., Südhof, T. C., & Malenka, R. C. (2011). The neurexin ligands, neuroligins and leucine-rich repeat transmembrane proteins, perform convergent and divergent synaptic functions in vivo. Proceedings of the National Academy of Sciences, 108(40), 16502â16509.
References
34
Referenced
121
10.1016/0092-8674(95)90396-8
10.1126/science.1621094
10.1016/j.neuron.2005.08.026
10.1016/j.neuron.2006.06.005
10.1016/j.neuron.2009.12.012
10.1016/j.neuron.2009.12.019
10.1523/JNEUROSCI.0470-10.2010
10.1016/S0092-8674(00)80877-6
10.1126/science.1107470
10.1016/j.neuron.2007.05.029
10.1016/j.neuron.2009.01.017
10.1038/nn.2825
10.1016/j.neuron.2006.09.003
10.1073/pnas.0803448105
10.1073/pnas.1001084107
10.1038/nature01755
10.1016/j.neuron.2006.09.012
10.1083/jcb.201101072
10.1073/pnas.96.3.1100
10.1016/S0888-7543(03)00030-2
10.1111/j.1460-9568.2007.05842.x
10.1078/0171-9335-00410
10.1038/368144a0
10.1016/j.neuron.2007.07.035
10.1002/1098-1063(2000)10:5<501::AID-HIPO1>3.0.CO;2-T
10.1038/35039075
10.1016/j.tcb.2007.07.005
10.1126/science.277.5331.1511
10.1016/j.cell.2008.10.008
10.1073/pnas.1111093108
10.1038/nature07456
10.1523/JNEUROSCI.3129-09.2010
10.1038/nprot.2006.450
10.1523/JNEUROSCI.2798-07.2007
Dates
Type | When |
---|---|
Created | 13 years, 10 months ago (Sept. 28, 2011, 1:20 a.m.) |
Deposited | 3 years, 4 months ago (April 12, 2022, 9:18 p.m.) |
Indexed | 2 months, 3 weeks ago (June 5, 2025, 4:06 p.m.) |
Issued | 13 years, 11 months ago (Sept. 27, 2011) |
Published | 13 years, 11 months ago (Sept. 27, 2011) |
Published Online | 13 years, 11 months ago (Sept. 27, 2011) |
Published Print | 13 years, 10 months ago (Oct. 4, 2011) |
@article{Soler_Llavina_2011, title={The neurexin ligands, neuroligins and leucine-rich repeat transmembrane proteins, perform convergent and divergent synaptic functions in vivo}, volume={108}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.1114028108}, DOI={10.1073/pnas.1114028108}, number={40}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Soler-Llavina, Gilberto J. and Fuccillo, Marc V. and Ko, Jaewon and Südhof, Thomas C. and Malenka, Robert C.}, year={2011}, month=sep, pages={16502–16509} }