Abstract
Classical cadherin-mediated interactions between axons and dendrites are critical to target selection and synapse assembly. However, the molecular mechanisms by which these interactions are controlled are incompletely understood. In the Drosophila visual system, N-cadherin is required in both photoreceptor (R cell) axons and their targets to mediate stabilizing interactions required for R cell target selection. Here we identify the scaffolding protein Liprin-alpha as a critical component in this process. We isolated mutations in Liprin-alpha in a genetic screen for mutations affecting the pattern of synaptic connections made by R1-R6 photoreceptors. Using eye-specific mosaics, we demonstrate a previously undescribed, axonal function for Liprin-alpha in target selection: Liprin-alpha is required to be cell-autonomous in all subtypes of R1-R6 cells for their axons to reach their targets. Because Liprin-alpha, the receptor tyrosine phosphatase LAR, and N-cadherin share qualitatively similar mutant phenotypes in R1-R6 cells and are coexpressed in R cells and their synaptic targets, we infer that these three genes act at the same step in the targeting process. However, unlike N-cadherin, neither Liprin-alpha nor LAR is required postsynaptically for R cells to project to their correct targets. Thus, these two proteins, unlike N-cadherin, are functionally asymmetric between axons and dendrites. We propose that the adhesive mechanisms that link pre- and postsynaptic cells before synapse formation may be differentially regulated in these two compartments.
