SLITKR1 is highly expressed in the central nervous system. It plays a critical part in regulating synapse formation between hippocampal neurons and in differentiation of synapses, helping in neuronal outgrowth. It is expressed during embryonic stages and postnatally but expression decreases over time and is localized to the postsynaptic membrane. Overexpression of SLITKR1 promotes postsynaptic differentiation for excitatory and inhibitory synapses, but because of the localization only excitatory synapses are affected. Inhibition of SLITKR1 only reduces differentiation of excitatory synapses because of this. Interaction with LAR-RPTP Since they lack tyrosine phosphorylation motifs, SLITKR1 binds to LAR-RPTP through its LRR1 region in order to differentiate synapses. The LRR2 domain's function is not clearly understood yet but it is hypothesised that it is for dimerization to the cell surface. LAR-RPTP binds to the LRR1 region through its PTPδ Ig region, with 3 separate binding sites in a 1:1 binding ratio. Ig1 binds through electrostatic and hydrophobic interactions, Ig2 binds through ionic and hydrogen bonds, and Ig2 binds through hydrogen bonding. The unique properties on the concave surface are what determine which LAR-RPTP binds to it. If the proper LAR-RPTP is not bound to the LRR1 then synapse formation cannot occur, but bonding can still occur. Once they are bound properly, the complex is sufficient for synapse differentiation. Point mutations in the LRR1 region impaired differentiation as well but not binding.
SLITRK1
TAAR1
CSTX
AHDC1
PANO1
KCNE1
CLCN1
SMN1