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SALM4 suppresses excitatory synapse development by cis-inhibiting trans-synaptic SALM3–LAR adhesion

Article scientifique 2016 Anglais

Résumé

Synaptic adhesion molecules regulate various aspects of synapse development, function and plasticity. These functions mainly involve trans-synaptic interactions and positive regulations, whereas cis-interactions and negative regulation are less understood. Here we report that SALM4, a member of the SALM/Lrfn family of synaptic adhesion molecules, suppresses excitatory synapse development through cis inhibition of SALM3, another SALM family protein with synaptogenic activity. Salm4-mutant (Salm4(-/-)) mice show increased excitatory synapse numbers in the hippocampus. SALM4 cis-interacts with SALM3, inhibits trans-synaptic SALM3 interaction with presynaptic LAR family receptor tyrosine phosphatases and suppresses SALM3-dependent presynaptic differentiation. Importantly, deletion of Salm3 in Salm4(-/-) mice (Salm3(-/-); Salm4(-/-)) normalizes the increased excitatory synapse number. These results suggest that SALM4 negatively regulates excitatory synapses via cis inhibition of the trans-synaptic SALM3-LAR adhesion.

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Lie, E., Ko, J., Choi, S., Roh, J., Cho, Y., Noh, R., Kim, D., Li, Y., Kang, H., Choi, T., Nam, J., Mah, W., Lee, D., Lee, S., Kim, H., Kim, H., Choi, S., Um, J., Kang, M., Bae, Y., Ko, J., Kim, E. (2016). SALM4 suppresses excitatory synapse development by cis-inhibiting trans-synaptic SALM3–LAR adhesion. https://doi.org/10.1038/ncomms12328

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Auteur(s)

Eunkyung Lie Ji Seung Ko Su‐Yeon Choi Junyeop Daniel Roh Yi Sul Cho Ran Noh Doyoun Kim Yan Li Hyeyeon Kang Tae-Yong Choi Jungyong Nam Won Mah Dongmin Lee Seong-Gyu Lee Ho Min Kim Hyun Kim Se‐Young Choi Ji Won Um Myoung‐Goo Kang Yong Chul Bae Jaewon Ko Eunjoon Kim

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