A Role for the Caenorhabditis Elegans Adenylate Forming Domain Protein Disco-Interacting Protein 2 (DIP-2) in the Maintenance of Neuron Morphology

Abstract

Post-developmentally, neurons are very long lived and, while shown to becapable of plasticity-promoting remodeling of dendritic structures, are thought tomaintain relatively stable morphologies over long animal lifespans. The molecularmechanisms that maintain neuronal morphology remain poorly understood. Membersof the highly conserved DIP2 protein family contain an N-terminal DNAmethyltransferase-associated protein 1 (DMAP1) binding domain and two adenylate-forming (AFD) domains. Using two loss-of-function alleles, we show that DIP-2 acts tomaintain neuronal morphology in C. elegans. dip-2 mutants display a progressiveincrease in ectopic neurite sprouting and branching post-development. DIP-2 acts in aDMAP1 binding-domain-independent manner to maintain neuronal morphology post-developmentally and DIP-2 overexpression can suppress the normal increase inneuronal sprouting defects observed in aging worms. Endogenous DIP-2 is widelyexpressed in neuronal and epithelial tissue but acts cell-autonomously in neurons.Finally, dip-2 neuronal defects are modified by loss of insulin/IGF-1 signalling (IIS) andDIP-2 acts in parallel with the SAX-2/Furry-SAX-1/NDR kinase pathway to regulateneuronal morphology