title: Complex interactions amongst N-cadherin, DLAR, and Liprin-alpha regulate Drosophila photoreceptor axon targeting.
abstract: The formation of stable adhesive contacts between pre- and post-synaptic neurons represents the initial step in synapse assembly. The cell adhesion molecule N-cadherin, the receptor tyrosine phosphatase DLAR, and the scaffolding molecule Liprin-alpha play critical, evolutionarily conserved roles in this process. However, how these proteins signal to the growth cone and are themselves regulated remains poorly understood. Using Drosophila photoreceptors (R cells) as a model, we evaluate genetic and physical interactions among these three proteins. We demonstrate that DLAR function in this context is independent of phosphatase activity but requires interactions mediated by its intracellular domain. Genetic studies reveal both positive and, surprisingly, inhibitory interactions amongst all three genes. These observations are corroborated by biochemical studies demonstrating that DLAR physically associates via its phosphatase domain with N-cadherin in Drosophila embryos. Together, these data demonstrate that N-cadherin, DLAR, and Liprin-alpha function in a complex to regulate adhesive interactions between pre- and post-synaptic cells and provide a novel mechanism for controlling the activity of Liprin-alpha in the developing growth cone.
authors.affiliation: Department of Neurobiology, 299 W. Campus Drive, Stanford University, Stanford, CA 94305, USA.
authors.forename: Saurabh
authors.initials: S
authors.lastname: Prakash
authors.forename: Helen M
authors.initials: HM
authors.lastname: McLendon
authors.forename: Catherine I
authors.initials: CI
authors.lastname: Dubreuil
authors.forename: Aurnab
authors.initials: A
authors.lastname: Ghose
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hwa
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Dennehy
authors.forename: Katharine M H
authors.initials: KM
authors.lastname: Tomalty
authors.forename: Kelsey L
authors.initials: KL
authors.lastname: Clark
authors.forename: David
authors.initials: D
authors.lastname: Van Vactor
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Clandinin
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D017956:Photoreceptor Cells, Invertebrate / Q000378:metabolism*; D011485:Protein Binding; D054557:Receptor-Like Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism
chemical_list: D015820:Cadherins; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; C490600:Liprin-alpha protein, Drosophila; D010750:Phosphoproteins; D049452:Green Fluorescent Proteins; C117978:Lar protein, Drosophila; D054557:Receptor-Like Protein Tyrosine Phosphatases