Our nervous system is a network of neurons connected through billions of synapses, allowing information to be transferred throughout the body. To form neural circuits, neurons must identify their correct synaptic partners among the many neurites in a target region, in a process called synaptic partner recognition (SPR). Elucidating the mechanisms of this critical and understudied process may provide better understanding of neurological disorders. Utilizing the trans-synaptic marker Neuroligin 1-mediated GFP Reconstitution Across Synaptic Partners (NLG-1 GRASP), which fluorescently labels specific synapses in live animals, and a circuit-specific behavioral assay to assess circuit function, our group previously found that the UNC-6/Netrin ligand and its receptor, UNC-40/Deleted in Colorectal Cancer (DCC), regulate SPR between PHB sensory neurons and AVA interneurons. In addition, our group previously demonstrated that the receptor protein tyrosine phosphatase (RPTP)
clr-1 acts with UNC-6/Netrin and UNC-40/DCC to mediate this process.
clr-1/RPTPs have immunoglobulin-like and fibronectin III domains, similar to the Leukocyte common Antigen-Related protein (LAR) family RPTPs, which have well-studied presynaptic roles in synaptogenesis, and less-understood postsynaptic roles. We found that
unc-6/Netrin and
clr-1/RPTP act in AVA interneurons, while
unc-40/DCC acts in PHB sensory neurons. However, the pathway downstream of
clr-1/RPTP in presumptive postsynaptic cells has not yet been elucidated. Here, we demonstrate that
syd-2/Liprin-? has a reduction in PHB-AVA synapses. In addition,
syd-2/+;
clr-1/+ trans-heterozygotes have a significant reduction in NLG-1 GRASP intensity, consistent with a role in the same pathway. This is consistent with studies in many organisms that indicate Liprin-? interacts with LAR family RPTPs. We are currently testing additional homologs of RPTP interactors for roles in SPR. We believe that this is a powerful system in which to understand the roles of LAR family members in postsynaptic cells, and identify their interactors.