Synaptic organizer: Slitrks and type IIa receptor protein tyrosine phosphatases

• Published in: Current opinion in structural biology 2019-02, Vol.54, p.95-103
• Main Authors: Won, Seoung Youn, Lee, Pedro, Kim, Ho Min
• Format: Article
• Language: English
• Subjects: Animals; Humans; Membrane Proteins - chemistry; Membrane Proteins - metabolism; Protein Tyrosine Phosphatases - chemistry; Protein Tyrosine Phosphatases - metabolism; Synapses - metabolism
• ISSN: 0959-440X; 1879-033X
• DOI: 10.1016/j.sbi.2019.01.010

•Slitrk family members are LRR-containing synaptic adhesion molecules highly expressed in the CNS.•Slitrks exert synaptogenic activity through interactions with specific members of the presynaptic type IIa RPTP family.•Type IIa RPTP bind to Slitrks in a splicing insert-dependent manner.•Higher-order clustering of type IIa RPTP/Slitrks complexes is necessary for their synaptogenic activity. 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.