Splicing-Dependent Trans-synaptic SALM3–LAR-RPTP Interactions Regulate Excitatory Synapse Development and Locomotion

• Main Authors: Yan Li, Peng Zhang, Tae-Yong Choi, Sook Kyung Park, Hanwool Park, Eun-Jae Lee, Dongsoo Lee, Junyeop Daniel Roh, Won Mah, Ryunhee Kim, Yangsik Kim, Harah Kwon, Yong Chul Bae, Se-Young Choi, Ann Marie Craig, Eunjoon Kim
• Format: Article
• Language: English
• Published: Elsevier 2015-09-01
• Series: Cell Reports
• Online Access: http://www.sciencedirect.com/science/article/pii/S221112471500858X

Synaptic adhesion molecules regulate diverse aspects of synapse development and plasticity. SALM3 is a PSD-95-interacting synaptic adhesion molecule known to induce presynaptic differentiation in contacting axons, but little is known about its presynaptic receptors and in vivo functions. Here, we identify an interaction between SALM3 and LAR family receptor protein tyrosine phosphatases (LAR-RPTPs) that requires the mini-exon B splice insert in LAR-RPTPs. In addition, SALM3-dependent presynaptic differentiation requires all three types of LAR-RPTPs. SALM3 mutant (Salm3−/−) mice display markedly reduced excitatory synapse number but normal synaptic plasticity in the hippocampal CA1 region. Salm3−/− mice exhibit hypoactivity in both novel and familiar environments but perform normally in learning and memory tests administered. These results suggest that SALM3 regulates excitatory synapse development and locomotion behavior.