A complement factor H homolog, heparan sulfation, and syndecan maintain inversin compartment boundaries in C. elegans cilia

Natalie Acker, Harold Smith, Claire Devine, Sharon L. Oltjen, Sofia Tsiropoulou, Zeljka Smit-McBride, Karen Lange, Oliver E. Blacque, Joanne A. Matsubara, Andrew Gordus, Andy Golden, Bruce E. Vogel

Research output: Contribution to journalArticlepeer-review


Age-related macular degeneration (AMD) is a leading cause of blindness among the elderly. Canonical disease models suggest that defective interactions between complement factor H (CFH) and cell surface heparan sulfate (HS) result in increased alternative complement pathway activity, cytolytic damage, and tissue inflammation in the retina. Although these factors are thought to contribute to increased disease risk, multiple studies indicate that noncanonical mechanisms that result from defective CFH and HS interaction may contribute to the progression of AMD as well. A total of 60 ciliated sensory neurons in the nematode Caenorhabditis elegans detect chemical, olfactory, mechanical, and thermal cues in the environment. Here, we find that a C. elegans CFH homolog localizes on CEP mechanosensory neuron cilia where it has noncanonical roles in maintaining inversin/NPHP-2 within its namesake proximal compartment and preventing inversin/NPHP-2 accumulation in distal cilia compartments in aging adults. CFH localization and maintenance of inversin/NPHP-2 compartment integrity depend on the HS 3-O sulfotransferase HST-3.1 and the transmembrane proteoglycan syndecan/SDN-1. Defective inversin/NPHP-2 localization in mouse and human photoreceptors with CFH mutations indicates that these functions and interactions may be conserved in vertebrate sensory neurons, suggesting that previously unappreciated defects in cilia structure may contribute to the progressive photoreceptor dysfunction associated with CFH loss-of-function mutations in some AMD patients.

Original languageEnglish (US)
Article numbere2016698118
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number16
StatePublished - Apr 20 2021


  • Cilia
  • Complement factor H
  • Heparan sulfate
  • Inversin
  • Syndecan

ASJC Scopus subject areas

  • General


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