TY - JOUR
T1 - Neurexins, neuroligins and LRRTMs: synaptic adhesion getting fishy.
T2 - Journal of Neurochemistry
AU - Wright, Gavin J
AU - Washbourne, Philip
PY - 2011
Y1 - 2011
N2 - Recent studies have identified the leucine rich repeat protein LRRTM2 as a post-synaptic ligand of Neurexins. Neurexins also bind the post-synaptic adhesion molecules, Neuroligins. All three families of genes have been implicated in the etiologies of neurodevelopmental disorders, specifically autism spectrum disorders and schizophrenia. Does the binding promiscuity of Neurexins now suggest complex cooperativity or redundancy at the synapse? While recent studies in primary neuronal cultures and also systematic extracellular protein interaction screens suggest summative effects of these systems, we propose that studying these interactions in the developing zebrafish embryo or larvae may shed more light on their functions during synaptogenesis in vivo. These gene families have recently been extensively characterized in zebrafish, demonstrating high sequence conservation with the human genes. The simpler circuitry of the zebrafish, together with the characterization of the expression patterns down to single, identifiable neurons and the ability to knock-down or over-express multiple genes in a rapid way lend themselves to dissecting complex interaction pathways. Furthermore, the capability of performing high-throughput drug screens suggests that these small vertebrates may prove extremely useful in identifying pharmacological approaches to treating autism spectrum disorders. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.
AB - Recent studies have identified the leucine rich repeat protein LRRTM2 as a post-synaptic ligand of Neurexins. Neurexins also bind the post-synaptic adhesion molecules, Neuroligins. All three families of genes have been implicated in the etiologies of neurodevelopmental disorders, specifically autism spectrum disorders and schizophrenia. Does the binding promiscuity of Neurexins now suggest complex cooperativity or redundancy at the synapse? While recent studies in primary neuronal cultures and also systematic extracellular protein interaction screens suggest summative effects of these systems, we propose that studying these interactions in the developing zebrafish embryo or larvae may shed more light on their functions during synaptogenesis in vivo. These gene families have recently been extensively characterized in zebrafish, demonstrating high sequence conservation with the human genes. The simpler circuitry of the zebrafish, together with the characterization of the expression patterns down to single, identifiable neurons and the ability to knock-down or over-express multiple genes in a rapid way lend themselves to dissecting complex interaction pathways. Furthermore, the capability of performing high-throughput drug screens suggests that these small vertebrates may prove extremely useful in identifying pharmacological approaches to treating autism spectrum disorders. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.
U2 - 10.1111/j.1471-4159.2010.07141.x
DO - 10.1111/j.1471-4159.2010.07141.x
M3 - Article
VL - 117
SP - 765
EP - 778
JO - J Neurochem
JF - J Neurochem
IS - 5
ER -