GRDN-1/Girdin regulates dendrite morphogenesis and cilium position in two specialized sensory neuron types in C. elegans

• DOI: 10.1016/j.ydbio.2020.12.022
• Publication Date: 2021-01-17T02:15:32Z
• Authors: Inna Nechipurenko; Sofia Lavrentyeva; Piali Sengupta
• Keywords: 0301 basic medicine; Sensory Receptor Cells; Neurogenesis; Microfilament Proteins; Kinesins; Cell Cycle Proteins; Dendrites; Cadherins; Axons; Basal Bodies; Animals, Genetically Modified; 03 medical and health sciences; Gene Knockdown Techniques; Mutation; Animals; Cilia; CRISPR-Cas Systems; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Wnt Signaling Pathway; Glycoproteins

Primary cilia are located at the dendritic tips of sensory neurons and house the molecular machinery necessary for detection and transduction of sensory stimuli. The mechanisms that coordinate dendrite extension with cilium position during sensory neuron development are not well understood. Here, we show that GRDN-1, the Caenorhabditis elegans ortholog of the highly conserved scaffold and signaling protein Girdin/GIV, regulates both cilium position and dendrite extension in the postembryonic AQR and PQR gas-sensing neurons. Mutations in grdn-1 disrupt dendrite outgrowth and mislocalize cilia to the soma or proximal axonal segments in AQR, and to a lesser extent, in PQR. GRDN-1 is localized to the basal body and regulates localization of HMR-1/Cadherin to the distal AQR dendrite. However, knockdown of HMR-1 and/or loss of SAX-7/LICAM, molecules previously implicated in sensory dendrite development in C. elegans, do not alter AQR dendrite morphology or cilium position. We find that GRDN-1 localization in AQR is regulated by UNC-116/Kinesin-1, and that correspondingly, unc-116 mutants exhibit severe AQR dendrite outgrowth and cilium positioning defects. In contrast, GRDN-1 and cilium localization in PQR is modulated by LIN-44/Wnt signaling. Together, these findings identify upstream regulators of GRDN-1, and describe new cell-specific roles for this multifunctional protein in sensory neuron development.