title: Differential dynamics and activity-dependent regulation of alpha- and beta-neurexins at developing GABAergic synapses.
abstract: Neurexins (NRXs) and neuroligins are key synaptic adhesion molecules that also recruit synaptic signaling machineries. Neurexins consist of α- and β-isoforms, but how they couple synaptic transmission and adhesion to regulate activity-dependent synapse development remains unclear, in part because of poor understanding of their cell biology and regulation in the relevant neurons. Here, we examined the subaxonal localization, dynamics, and regulation of NRX1α and NRX1β in cortical perisomatic inhibitory synapses. Both isoforms are delivered to presynaptic terminals but show significant and different turnover rate at the membrane. Although NRX1α is highly diffuse along developing axons and filopodia, NRX1β is strictly anchored at terminals through binding to postsynaptic ligands. The turnover rate of NRX1β is attenuated by neural activity and presynaptic GABA(B) receptors. NRXs, thus, are intrinsically dynamic but are stabilized by local transmitter release. Such an activity-adjusted adhesion system seems ideally suited to rapidly explore and validate synaptic partners guided by synaptic transmission.
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Fu
authors.forename: Z Josh
authors.initials: ZJ
authors.lastname: Huang
mesh_terms: D000818:Animals; D019470:Biolistics; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D036681:Fluorescence Recovery After Photobleaching; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007395:Interneurons / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D056004:Molecular Dynamics Simulation; D019579:Neocortex / Q000166:cytology / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010320:Parvalbumins / Q000378:metabolism; D017729:Presynaptic Terminals / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D018080:Receptors, GABA-B / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D046509:Tissue Culture Techniques; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D009419:Nerve Tissue Proteins; D010320:Parvalbumins; D020033:Protein Isoforms; D018080:Receptors, GABA-B; D049452:Green Fluorescent Proteins; C086959:neurexin Ibeta; D005680:gamma-Aminobutyric Acid; D002118:Calcium