Following the migration of the axonal growth cone to its target area, the 
initial axo-dendritic contact needs to be transformed into a functional synapse. 
This multi-step process relies on overlapping but distinct combinations of 
molecules that confer synaptic identity. Slitrk molecules are transmembrane 
proteins that are highly expressed in the central nervous system. We found that 
two members of the Slitrk family, Slitrk1 and Slitrk2, can regulate synapse 
formation between hippocampal neurons. Slitrk1 is enriched in postsynaptic 
fractions and is localized to excitatory synapses. Overexpression of Slitrk1 and 
Slitrk2 in hippocampal neurons increased the number of synaptic contacts on 
these neurons. Furthermore, decreased expression of Slitrk1 in hippocampal 
neurons led to a reduction in the number of excitatory, but not inhibitory, 
synapses formed in hippocampal neuron cultures. In addition, we demonstrate that 
different leucine rich repeat domains of the extracellular region of Slitrk1 are 
necessary to mediate interactions with Slitrk binding partners of the LAR 
receptor protein tyrosine phosphatase family, and to promote dimerization of 
Slitrk1. Altogether, our results demonstrate that Slitrk family proteins 
regulate synapse formation.