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Convertase-dependent regulation of membrane-tethered and secreted ligands tunes dendrite adhesion.

Nelson J Ramirez-Suarez | Helen M Belalcazar | Maisha Rahman | Meera Trivedi | Leo T H Tang | Hannes E Bülow
Development (Cambridge, England) | 2023

During neural development, cellular adhesion is crucial for interactions among and between neurons and surrounding tissues. This function is mediated by conserved cell adhesion molecules, which are tightly regulated to allow for coordinated neuronal outgrowth. Here, we show that the proprotein convertase KPC-1 (homolog of mammalian furin) regulates the Menorin adhesion complex during development of PVD dendritic arbors in Caenorhabditis elegans. We found a finely regulated antagonistic balance between PVD-expressed KPC-1 and the epidermally expressed putative cell adhesion molecule MNR-1 (Menorin). Genetically, partial loss of mnr-1 suppressed partial loss of kpc-1, and both loss of kpc-1 and transgenic overexpression of mnr-1 resulted in indistinguishable phenotypes in PVD dendrites. This balance regulated cell-surface localization of the DMA-1 leucine-rich transmembrane receptor in PVD neurons. Lastly, kpc-1 mutants showed increased amounts of MNR-1 and decreased amounts of muscle-derived LECT-2 (Chondromodulin II), which is also part of the Menorin adhesion complex. These observations suggest that KPC-1 in PVD neurons directly or indirectly controls the abundance of proteins of the Menorin adhesion complex from adjacent tissues, thereby providing negative feedback from the dendrite to the instructive cues of surrounding tissues.

Pubmed ID: 37721334

Research resources used in this publication

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Associated grants

  • Agency: NINDS NIH HHS, United States
    Id: R21 NS081505
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS129992
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS096672
  • Agency: NINDS NIH HHS, United States
    Id: F31 NS100370
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM149364
  • Agency: NICHD NIH HHS, United States
    Id: P30 HD071593
  • Agency: NINDS NIH HHS, United States
    Id: F31 NS111939
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM007288

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