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

Area of Science:

• Neuroscience
• Molecular Biology
• Synaptic Plasticity

Background:

• Synaptic adhesion molecules are crucial for synapse formation and function.
• SALM3, a known PSD-95 interactor, induces presynaptic differentiation, but its receptors and in vivo roles are unclear.

Purpose of the Study:

• To identify presynaptic receptors for SALM3.
• To investigate the in vivo function of SALM3 in synapse development and behavior.

Main Methods:

• Yeast two-hybrid screening to identify SALM3 interacting proteins.
• Co-immunoprecipitation assays to confirm interactions.
• Generation and behavioral analysis of SALM3 knockout mice (Salm3(-/-)).

Main Results:

• SALM3 interacts with LAR family receptor protein tyrosine phosphatases (LAR-RPTPs), dependent on the mini-exon B splice insert.
• Presynaptic differentiation induced by SALM3 requires LAR-RPTPs.
• Salm3(-/-) mice show a significant reduction in excitatory synapse numbers in the hippocampus.
• Salm3(-/-) mice exhibit hypoactivity but normal learning and memory.

Conclusions:

• SALM3 functions in vivo to regulate excitatory synapse development.
• SALM3 plays a role in controlling locomotion behavior.
• The interaction with LAR-RPTPs is critical for SALM3's function in synapse development.