Reference - Detail
| RRC ID | 87994 |
|---|---|
| Author | Reddy AR, Machera SJ, Cook ZT, Deng H, Nawrocka WI, Özkan E, Shen K. |
| Title | A dendritic guidance receptor functions in both ligand dependent and independent modes. |
| Journal | PLoS Genet |
| Abstract |
The formation of an appropriately shaped dendritic arbor is critical for a neuron to receive information. Dendritic morphogenesis is a dynamic process involving growth, branching, and retraction. How the growth and stabilization of dendrites are coordinated at the molecular level remains a key question in developmental neurobiology. The highly arborized and stereotyped dendritic arbors of the Caenorhabditis elegans PVD neuron are shaped by the transmembrane DMA-1 receptor through its interaction with a tripartite ligand complex consisting of SAX-7/L1CAM, MNR-1/FAM151B, and LECT-2/LECT2. However, receptor null mutants exhibit strongly reduced dendrite outgrowth, whereas ligand null mutants show disordered branch patterns, suggesting a ligand-independent function of the receptor. To test this idea, we identified point mutations in dma-1 that disrupt receptor-ligand binding and introduced corresponding mutations into the endogenous gene. We show that the ligand-free receptor is sufficient to drive robust, disordered dendritic branch formation but results in a complete loss of arbor shape. This disordered outgrowth program utilizes similar downstream effectors as the stereotyped outgrowth program, further arguing that ligand binding is not necessary for outgrowth. Finally, we demonstrate that ligand binding is required to maintain higher-order dendrites after development is complete. Taken together, our findings support a surprising model in which ligand-free and ligand-bound DMA-1 receptors have distinct functions: the ligand-free receptor promotes stochastic outgrowth and branching, whereas the ligand-bound receptor guides stereotyped dendrite morphology by stabilizing arbors at target locations. |
| Volume | 21(12) |
| Pages | e1011942 |
| Published | 2025-12-1 |
| DOI | 10.1371/journal.pgen.1011942 |
| PII | PGENETICS-D-25-00441 |
| PMID | 41348823 |
| PMC | PMC12680191 |
| MeSH | Animals Caenorhabditis elegans* / genetics Caenorhabditis elegans* / growth & development Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Cell Adhesion Molecules / genetics Cell Adhesion Molecules / metabolism Dendrites* / genetics Dendrites* / metabolism Dendrites* / physiology Intercellular Signaling Peptides and Proteins / genetics Intercellular Signaling Peptides and Proteins / metabolism Ligands Membrane Proteins* / genetics Membrane Proteins* / metabolism Neural Cell Adhesion Molecules Neurogenesis / genetics Neurons / metabolism |
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 1 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| C.elegans | tm1556 |