Synaptic organizer: Slitrks and type IIa receptor protein tyrosine phosphatases.

Slit-like and Trk-like (Slitrk) family members are leucine-rich repeat (LRR)-containing neuronal transmembrane proteins. Slitrks have been highlighted as key synapse organizers at neuronal synapses through interactions with specific members of the presynaptic type IIa receptor protein tyrosine phosphatase (RPTP) family. Recent structural studies on type IIa RPTP/Slitrk1 complexes have unveiled molecular insights into their binding selectivity and have established the role of higher-order receptor clustering in their synaptogenic activity. Here, we will discuss key structural aspects of Slitrk interactions with type IIa RPTP family members, the biological roles of Slitrks in neurons, and our current knowledge of SLITRK mutations in human diseases.