Complex interactions amongst N-cadherin, DLAR, and Liprin-α 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-α 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-α 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-α in the developing growth cone.

The genetic basis for variation in resistance to infection in the Drosophila melanogaster genetic reference panel

“…Likewise, Lar is involved in multiple processes involving cadherin and adhesive interactions [42]. The cadherin Dystroglycan ( Dg ) is associated with stress responses in Drosophila and humans [43].…”

The receptor tyrosine phosphatase Lar regulates adhesion between Drosophila male germline stem cells and the niche

“…Lar also localizes to adherens junctions in epithelial cells (Aicher et al, 1997) and in neuronal synapses that are enriched in cadherin-catenin complexes (Dunah et al, 2005). Lar physically associates with the cadherin-catenin complex in cultured cells (Aicher et al, 1997;Kypta et al, 1996;Muller et al, 1999) and with N-cadherin in Drosophila embryos (Prakash et al, 2009).…”

A Network of Cadherin-Mediated Interactions Polarizes Growth Cones to Determine Targeting Specificity

“…The classical cadherin Ncad, the receptor tyrosine phosphatase LAR and the adaptor protein Liprin-α are critically involved in the extension of R cell growth cones toward their target column (Choe et al, 2006; Lee et al, 2001; Prakash et al, 2005; Prakash et al, 2009). Ncad is expressed both in R cells and LMCs and mediates interactions between these two cell types; R cells that lack Ncad, LAR or Liprin-α frequently fail to extend.…”