Affinity Requirements For Control Of Synaptic Targeting And Neuronal Cell Survival By Heterophilic IgSF Cell Adhesion Molecules

Abstract

Neurons in the developing brain express many different cell adhesion molecules (CAMs) on their surfaces, and CAM interactions are essential for the determination of synaptic connectivity patterns. CAM binding affinities can vary by more than 200-fold, but the significance of affinity differences among CAMs is unknown. Here we provide a systematic characterization of the in vivo consequences of altering CAM affinity. Interactions between DIP-α and its binding partners Dpr6 and Dpr10 control synaptic targeting and cell survival for Drosophila optic lobe neurons. We generated mutations that change DIP-α::Dpr10 binding affinity and introduced these into the endogenous loci. We show that cell survival and synaptic targeting have different affinity requirements, and that there is a threshold affinity required for targeting. Reducing affinity causes graded loss-of-function phenotypes, while increasing affinity rescues cells that would normally die. Affinity reduction can be compensated for by increasing gene copy number.