title: Dynamic mechanisms of neuroligin-dependent presynaptic terminal assembly in living cortical neurons.
abstract: BACKGROUND
  Synapse formation occurs when synaptogenic signals trigger coordinated development of pre and postsynaptic structures. One of the best-characterized synaptogenic signals is trans-synaptic adhesion. However, it remains unclear how synaptic proteins are recruited to sites of adhesion. In particular, it is unknown whether synaptogenic signals attract synaptic vesicle (SV) and active zone (AZ) proteins to nascent synapses or instead predominantly function to create sites that are capable of forming synapses. It is also unclear how labile synaptic proteins are at developing synapses after their initial recruitment. To address these issues, we used long-term, live confocal imaging of presynaptic terminal formation in cultured cortical neurons after contact with the synaptogenic postsynaptic adhesion proteins neuroligin-1 or SynCAM-1.
  
  
  RESULTS
  Surprisingly, we find that trans-synaptic adhesion does not attract SV or AZ proteins nor alter their transport. In addition, although neurexin (the presynaptic partner of neuroligin) typically accumulates over the entire region of contact between axons and neuroligin-1-expressing cells, SV proteins selectively assemble at spots of enhanced neurexin clustering. The arrival and maintenance of SV proteins at these sites is highly variable over the course of minutes to hours, and this variability correlates with neurexin levels at individual synapses.
  
  
  CONCLUSIONS
  Together, our data support a model of synaptogenesis where presynaptic proteins are trapped at specific axonal sites, where they are stabilized by trans-synaptic adhesion signaling.
authors.forename: Luke Ad
authors.initials: LA
authors.lastname: Bury
authors.affiliation: Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA. shasta.sabo@case.edu.
authors.forename: Shasta L
authors.initials: SL
authors.lastname: Sabo
mesh_terms: D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D017729:Presynaptic Terminals / Q000378:metabolism*; D021381:Protein Transport; D051381:Rats; D016708:Synaptophysin / Q000378:metabolism
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D009419:Nerve Tissue Proteins; D016708:Synaptophysin; C093438:neuroligin 1; C086959:neurexin Ibeta