Cameron, Sarah2026-07-142026-07-142026-042026-07-14http://hdl.handle.net/1993/39856Neurotransmission typically occurs when neurotransmitters, released by the presynapse, interact with receptors on the postsynapse. Interruptions in these interactions can lead to neurological disorders. Recently, these trans-synaptic interactions were found to involve synaptic adhesion molecules, modulating the activity of a subgroup of G protein-coupled receptors (GPCRs) known as the metabotropic glutamate receptors (mGluRs). A synaptic adhesion molecule called L1CAM has been found to interact with mGluR5. L1CAM is of particular interest because it is the known cause of L1 syndrome, a neurodevelopmental disorder that can cause hydrocephalus, spastic paraplegia, and intellectual disability. As a well-established drug target for neurological disorders, mGluR5, in complex with L1CAM, may have major implications in the etiology of L1 syndrome. We hypothesize that L1CAM is a trans-synaptic modulator of mGluR5. Co-immunoprecipitation experiments were conducted to detect binding of L1CAM, the synaptic adhesion molecule, to the receptors, mGluR5 and mGluR2 (a negative control), at the protein level. Trans-cellular signaling experiments were conducted to determine the functional response of the L1CAM-mGluR interaction at the cellular level. As a result, we found that L1CAM does complex with mGluR5 and not mGluR2. A functional response has not yet been seen, but it is possible that different experimental conditions are required to accurately reflect cell conditions in vivo. In future research, discovery of L1CAM-mGluR5 trans-cellular modulation would lead to further understanding of trans-synaptic interactions between mGluRs and synaptic adhesion molecules, and possibly further the understanding of the etiology of L1 syndrome. As an overarching objective of possible L1CAM-mGluR5 modulation, a therapeutic could be developed to rescue the interaction of L1CAM and mGluR5 in those with L1 syndrome.engL1CAMmGluR5L1 syndrome