title: Trans-synaptic Teneurin signalling in neuromuscular synapse organization and target choice.
abstract: Synapse assembly requires trans-synaptic signals between the pre- and postsynapse, but our understanding of the essential organizational molecules involved in this process remains incomplete. Teneurin proteins are conserved, epidermal growth factor (EGF)-repeat-containing transmembrane proteins with large extracellular domains. Here we show that two Drosophila Teneurins, Ten-m and Ten-a, are required for neuromuscular synapse organization and target selection. Ten-a is presynaptic whereas Ten-m is mostly postsynaptic; neuronal Ten-a and muscle Ten-m form a complex in vivo. Pre- or postsynaptic Teneurin perturbations cause severe synapse loss and impair many facets of organization trans-synaptically and cell autonomously. These include defects in active zone apposition, release sites, membrane and vesicle organization, and synaptic transmission. Moreover, the presynaptic microtubule and postsynaptic spectrin cytoskeletons are severely disrupted, suggesting a mechanism whereby Teneurins organize the cytoskeleton, which in turn affects other aspects of synapse development. Supporting this, Ten-m physically interacts with α-Spectrin. Genetic analyses of teneurin and neuroligin reveal that they have differential roles that synergize to promote synapse assembly. Finally, at elevated endogenous levels, Ten-m regulates target selection between specific motor neurons and muscles. Our study identifies the Teneurins as a key bi-directional trans-synaptic signal involved in general synapse organization, and demonstrates that proteins such as these can also regulate target selection.
authors.affiliation: Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, USA. tmosca@stanford.edu
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Mosca
authors.forename: Weizhe
authors.initials: W
authors.lastname: Hong
authors.forename: Vardhan S
authors.initials: VS
authors.lastname: Dani
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Favaloro
authors.forename: Liqun
authors.initials: L
authors.lastname: Luo
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D029721:Drosophila Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism*; D005786:Gene Expression Regulation; D007814:Larva / Q000166:cytology / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009132:Muscles / Q000166:cytology / Q000378:metabolism; D009469:Neuromuscular Junction / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission; D019063:Tenascin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D015816:Cell Adhesion Molecules, Neuronal; D029721:Drosophila Proteins; D008869:Microtubule-Associated Proteins; C491321:Nrx protein, Drosophila; D011956:Receptors, Cell Surface; C470835:Ten-a protein, Drosophila; C089140:Ten-m protein, Drosophila; D019063:Tenascin; C409635:futsch protein, Drosophila; C093438:neuroligin 1