Complex interactions amongst N-cadherin, DLAR, and Liprin-alpha regulate Drosophila photoreceptor axon targeting.
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.
Prakash
Saurabh
S
Department of Neurobiology, 299 W. Campus Drive, Stanford University, Stanford, CA 94305, USA.
McLendon
Helen M
HM
Dubreuil
Catherine I
CI
Ghose
Aurnab
A
Hwa
Jennifer
J
Dennehy
Kelly A
KA
Tomalty
Katharine M H
KM
Clark
Kelsey L
KL
Van Vactor
David
D
Clandinin
Thomas R
TR
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
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