Neuroligin-Neurexin Interaction: Difference between revisions
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<StructureSection load='' size='500' side='right' caption='Structure of Neurexin and Neuroligin' scene=''> | <StructureSection load='' size='500' side='right' caption='Structure of Neurexin and Neuroligin' scene=''> | ||
Neurexins (NRXNs) and Neuroligins (NLGNs) are synaptic cell-adhesion molecules that connect presynaptic and postsynaptic neurons at synapses. NLGNs, of which NLGN1-5 are the best characterized, are endogenous NRXN ligands. (Chih) Upon binding NRXN, NLGNs mediate signaling across the synapse, and shape the properties of neural networks by specifying synaptic functions. (Sudhof) Early experiments proved that NLGNs function at synapses by showing that NLGNs expressed in non-neuronal cells can induce co-cultured neurons to form presynaptic specializations onto the non-neuronal cell. The same is true for NRXNs which formed postsynaptic specializations. (sudhof) Subsequent analysis of gene-knockout mice surprisingly revealed that NLGNS and NRXNs are essential for synaptic function and organization, but not synapse formation. (Katsuhiko) In effect, NRXNS and NLGNS shape synaptic efficacy and plasticity. (sudhof) | ''Neurexins'' (''NRXNs'') and ''Neuroligins'' (''NLGNs'') are synaptic cell-adhesion molecules that connect presynaptic and postsynaptic neurons at synapses. NLGNs, of which NLGN1-5 are the best characterized, are endogenous NRXN ligands. (Chih) Upon binding NRXN, NLGNs mediate signaling across the synapse, and shape the properties of neural networks by specifying synaptic functions. (Sudhof) Early experiments proved that NLGNs function at synapses by showing that NLGNs expressed in non-neuronal cells can induce co-cultured neurons to form presynaptic specializations onto the non-neuronal cell. The same is true for NRXNs which formed postsynaptic specializations. (sudhof) Subsequent analysis of gene-knockout mice surprisingly revealed that NLGNS and NRXNs are essential for synaptic function and organization, but not synapse formation. (Katsuhiko) In effect, NRXNS and NLGNS shape synaptic efficacy and plasticity. (sudhof) | ||
Experimental results from the past 10 years have revealed that loss of Neuroligin function has a selective reductive effect on inhibitory synapse function indicating that functional inhibitory synapses rely more heavily on neuroligins than do excitatory synapses.(Chih) This was an astonishing discovery as [[Autism Spectrum Disorders]] (ASDs) have long been attributed to perturbations in the Excitatory/Inhibitory (E/I) synaptic signal ratios within the brain. Knockdown studies have validated that the selective knockdown of NLGNs resulted in a significant imbalance of E/I transmission possibly altering oscillatory rhythms in the brain (katsuhiko) (chih) As Sudhof et al. point out, a major reason for the difficitulties in understanding cognitive diseases is that they arise from subtle changes in a subset of synapses as opposed to obvious impairment of all synapses in all circuits. (sudhof) The altered E/I ratios associated with NLGN disfunction may be an example of such a “subtle change”. Indeed, mice with loss-of function mutations in NLGN4 exhibit defecits in social interactions and commnication that are reminiscent of ASDs. (Jamain) Of particular interest are those NLGN3 mutations like R451C in which mice have the impaired social ability but elevated learning capacity manifestations reminiscent of “savant” syndrome. (Katsuhiko) In all, seven point mutations, two translocations and four large-scale deletions in the NRXN1 gene were detected in patients with autism (Sudhof). These mutations however were only found in a small perecentage of Autism patients and are occasionally present in non-symptomatic siblings. Thus, these mutations may only increase the chance of autism rather than actually causing it. (Fabrichny) | Experimental results from the past 10 years have revealed that loss of Neuroligin function has a selective reductive effect on inhibitory synapse function indicating that functional inhibitory synapses rely more heavily on neuroligins than do excitatory synapses.(Chih) This was an astonishing discovery as [[Autism Spectrum Disorders]] (ASDs) have long been attributed to perturbations in the Excitatory/Inhibitory (E/I) synaptic signal ratios within the brain. Knockdown studies have validated that the selective knockdown of NLGNs resulted in a significant imbalance of E/I transmission possibly altering oscillatory rhythms in the brain (katsuhiko) (chih) As Sudhof et al. point out, a major reason for the difficitulties in understanding cognitive diseases is that they arise from subtle changes in a subset of synapses as opposed to obvious impairment of all synapses in all circuits. (sudhof) The altered E/I ratios associated with NLGN disfunction may be an example of such a “subtle change”. Indeed, mice with loss-of function mutations in NLGN4 exhibit defecits in social interactions and commnication that are reminiscent of ASDs. (Jamain) Of particular interest are those NLGN3 mutations like R451C in which mice have the impaired social ability but elevated learning capacity manifestations reminiscent of “savant” syndrome. (Katsuhiko) In all, seven point mutations, two translocations and four large-scale deletions in the NRXN1 gene were detected in patients with autism (Sudhof). These mutations however were only found in a small perecentage of Autism patients and are occasionally present in non-symptomatic siblings. Thus, these mutations may only increase the chance of autism rather than actually causing it. (Fabrichny) | ||