气候变化领域集成服务门户(CCPortal): A complement factor H homolog, heparan sulfation, and syndecan maintain inversin compartment boundaries in C. elegans cilia

CCPortal

DOI	10.1073/pnas.2016698118
	A complement factor H homolog, heparan sulfation, and syndecan maintain inversin compartment boundaries in C. elegans cilia
	Acker N.; Smith H.; Devine C.; Oltjen S.L.; Tsiropoulou S.; Smit-McBride Z.; Lange K.; Blacque O.E.; Matsubara J.A.; Gordus A.; Golden A.; Vogel B.E.
发表日期	2021
ISSN	00278424
卷号	118 期号:16
英文摘要	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. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Cilia; Complement factor H; Heparan sulfate; Inversin; Syndecan
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/179800
作者单位	Center for Biomedical Engineering and Technology, University of Maryland, School of Medicine, University of Maryland, Baltimore, MD 21201, United States; Laboratory of Biochemistry and Genetics, National Institute of Diabetes, Digestive, and Kidney Diseases, NIH, Bethesda, MD 20892, United States; Department of Ophthalmology and Vision Science, Vitreoretinal Research Laboratory, University of California, Davis, CA 95616, United States; School of Biomolecular and Biomedical Research, UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland; Department of Ophthalmology and Visual Sciences, The University of British Columbia, Vancouver, BC V5Z 3N9, Canada; Department of Biology, The Johns Hopkins University, Baltimore, MD 21211, United States; Department of Physiology, University of Maryland, School of Medicine, University of Maryland, Baltimore, MD 21201, United States
推荐引用方式 GB/T 7714	Acker N.,Smith H.,Devine C.,et al. A complement factor H homolog, heparan sulfation, and syndecan maintain inversin compartment boundaries in C. elegans cilia[J],2021,118(16).
APA	Acker N..,Smith H..,Devine C..,Oltjen S.L..,Tsiropoulou S..,...&Vogel B.E..(2021).A complement factor H homolog, heparan sulfation, and syndecan maintain inversin compartment boundaries in C. elegans cilia.Proceedings of the National Academy of Sciences of the United States of America,118(16).
MLA	Acker N.,et al."A complement factor H homolog, heparan sulfation, and syndecan maintain inversin compartment boundaries in C. elegans cilia".Proceedings of the National Academy of Sciences of the United States of America 118.16(2021).