FIGURE 2.

Different splice variants of TENs regulate distinct synapse specifications. Alternative splicing is a molecular switch to regulate which binding partner TEN2 binds to, and what respective function TEN2 does. On the left side, the -SS isoform of TEN2 (empty star) interacts with LPHN. When it is co-expressed with FLRT, TEN2 isoform that lacks the splice insert induces excitatory postsynaptic differentiation. On the right side, TEN2 that includes the splice insert (full star) cannot interact with LPHN, but it can form trans-homodimers to mediate neural circuit-wiring and induces inhibitory synapses. The left and right sides of the TEN2 dimer represent excitatory and inhibitory synapses, respectively. The membranes, teneurin structure (Li et al., 2018) (PDB ID: 6CMX), and distance between the membranes are drawn to scale. Alternative splice site is shown by red star. Insert: Representative negative stain EM micrographs of TEN2 ECR(1-5) shows a TEN2 -SS cis-dimer. Yellow arrows indicate EGF repeats. Figure modified from Li et al. (2018).