title: A multi-protein receptor-ligand complex underlies combinatorial dendrite guidance choices inC. elegans.
abstract: Ligand receptor interactions instruct axon guidance during development. How dendrites are guided to specific targets is less understood. TheC. elegansPVD sensory neuron innervates muscle-skin interface with its elaborate dendritic branches. Here, we found that LECT-2, the ortholog of leukocyte cell-derived chemotaxin-2 (LECT2), is secreted from the muscles and required for muscle innervation by PVD. Mosaic analyses showed that LECT-2 acted locally to guide the growth of terminal branches. Ectopic expression of LECT-2 from seam cells is sufficient to redirect the PVD dendrites onto seam cells. LECT-2 functions in a multi-protein receptor-ligand complex that also contains two transmembrane ligands on the skin, SAX-7/L1CAM and MNR-1, and the neuronal transmembrane receptor DMA-1. LECT-2 greatly enhances the binding between SAX-7, MNR-1 and DMA-1. The activation of DMA-1 strictly requires all three ligands, which establishes a combinatorial code to precisely target and pattern dendritic arbors.
authors.affiliation: Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States.
authors.forename: Wei
authors.initials: W
authors.lastname: Zou
authors.affiliation: Department of Pharmacology, University of California, Davis, Davis, United States.
authors.forename: Ao
authors.initials: A
authors.lastname: Shen
authors.affiliation: Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States.
authors.forename: Xintong
authors.initials: X
authors.lastname: Dong
authors.affiliation: Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States.
authors.forename: Madina
authors.initials: M
authors.lastname: Tugizova
authors.affiliation: Department of Pharmacology, University of California, Davis, Davis, United States.
authors.forename: Yang K
authors.initials: YK
authors.lastname: Xiang
authors.affiliation: Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States.
authors.forename: Kang
authors.identifier: 0000-0003-4059-8249
authors.initials: K
authors.lastname: Shen
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D003712:Dendrites / Q000187:drug effects* / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008024:Ligands; D008565:Membrane Proteins / Q000378:metabolism; D046912:Multiprotein Complexes / Q000378:metabolism*; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; C569907:DMA-1 protein, C elegans; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; C585068:MNR-1 protein, C elegans; D008565:Membrane Proteins; D046912:Multiprotein Complexes; D039842:Neural Cell Adhesion Molecule L1; D019006:Neural Cell Adhesion Molecules; D011956:Receptors, Cell Surface; C501528:SAX-7 protein, C elegans
keywords: C. elegans; cell-cell adhesion; dendrite guidance; developmental biology; ligand-receptor interaction; neuroscience; stem cells