Neuroligin-induced presynaptic differentiation through SLM2-mediated splicing modifications of neurexin in cerebellar cultures

作者：Sato Yuji; Suzuki Satoko; Iijima Yoko; Iijima Takatoshi^*

来源：Biochemical and Biophysical Research Communications, 2017, 493(2): 1030-1036.

DOI：10.1016/j.bbrc.2017.09.097

• Alternative splicing
• GABAergic neuron
• Neurexin
• Neuroligin
• SLM2
• Synapse

Neurexins (NRXs) and neuroligins (NLs) play important roles in synapse specification. The alternatively spliced segment 4 (AS4) of NRX genes (Nrxn) is a critical element in selective trans-synaptic interactions. However, the role of splicing of NRXs and NLs in synapse specification is not fully understood. To investigate the exact role of splice-dependent NRX-NL interaction in the specification of glutamatergic and gamma-aminobutyric acid (GABA)-ergic synapses in the cerebellum, we evaluated the synaptogenic receptor activity of NL1/2/3 isoforms in a neuron-fibroblast co-culture system, in which the Nrxn AS4 segments are manipulated using SLM2, a selective and dominant regulator of AS4 splicing. We show that ectopic SLM2 expression (SLM2 E/E) causes marked skipping of exon 20 of AS4 in cerebellar neuron culture. Whereas NLs can induce VAMP2(+) presynaptic contacts from mainly glutamatergic neurons in both uninfected (control) and SLM2 E/E co-cultures, they induce VGAT(+) GABAergic contacts in the control culture, but not properly in the SLM2 E/E culture. Furthermore, Nrxn3 is responsible for the NL-induced assembly of GABAergic synapses in co-culture. Importantly, lentivirus-based expression of Nrxn3 containing exon 20 restores the reduced NL-induced GABAergic contacts in the SLM2 co-culture. Therefore, our findings may provide further insights into NRX-NL mediated synapse specification.

• 出版日期2017-11-18