气候变化领域集成服务门户(CCPortal): Ciliopathy genes are required for apical secretion of Cochlin, an otolith crystallization factor

CCPortal

DOI	10.1073/pnas.2102562118
	Ciliopathy genes are required for apical secretion of Cochlin, an otolith crystallization factor
	Leventea E.; Zhu Z.; Fang X.; Nikolaeva Y.; Markham E.; Hirst R.A.; van Eeden F.J.M.; Malicki J.J.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:28
英文摘要	Here, we report that important regulators of cilia formation and ciliary compartment–directed protein transport function in secretion polarity. Mutations in cilia genes cep290 and bbs2, involved in human ciliopathies, affect apical secretion of Cochlin, a major otolith component and a determinant of calcium carbonate crystallization form. We show that Cochlin, defective in human auditory and vestibular disorder, DFNA9, is secreted from small specialized regions of vestibular system epithelia. Cells of these regions secrete Cochlin both apically into the ear lumen and basally into the basal lamina. Basally secreted Cochlin diffuses along the basal surface of vestibular epithelia, while apically secreted Cochlin is incorporated into the otolith. Mutations in a subset of ciliopathy genes lead to defects in Cochlin apical secretion, causing abnormal otolith crystallization and behavioral defects. This study reveals a class of ciliary proteins that are important for the polarity of secretion and delineate a secretory pathway that regulates biomineralization. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Apical secretion; Cep290; Cochlin; Ear; Otolith
语种	英语
scopus关键词	4',6 diamidino 2 phenylindole; ab97051; acetic acid; acetone; adenosine diphosphate ribosylation factor; alcohol; brilliant blue g; buffer; calcium carbonate; cobalt; cochlin; complementary DNA; deionized water; edetic acid; enhanced green fluorescent protein; glutaraldehyde; gold; horseradish peroxidase; immunoglobulin G; methanol; osmium tetraoxide; paraformaldehyde; phosphate buffered saline; protein ZO1; pyroxylin; Rab11 protein; sodium chloride; tricaine; tubulin; von Willebrand factor; water; zebrafish protein; adult; anesthesia; animal experiment; animal model; animal tissue; antigen retrieval; Article; Bardet Biedl syndrome; behavior disorder; biomineralization; cell polarity; centrifugation; ciliopathy; cilium; confocal microscopy; CRISPR-CAS9 system; crystallization; DNA isolation; embryo development; epithelium; gene mutation; genotype; hearing impairment; immunohistochemistry; in situ hybridization; incubation time; inner ear; mass spectrometry; missense mutation; nonhuman; osmotic stress; otolith; phenotype; physiological stress; polyacrylamide gel electrophoresis; polymerase chain reaction; proteomics; radioimmunoprecipitation; Sanger sequencing; scanning electron microscopy; secretory pathway; sputter deposition; staining; stereomicroscopy; swimming; vestibular disorder; Western blotting; amino acid sequence; animal; ciliopathy; crystallization; epistasis; gene expression regulation; genetics; homozygote; metabolism; mutation; nucleotide sequence; otolithic membrane; zebra fish; Amino Acid Sequence; Animals; Bardet-Biedl Syndrome; Base Sequence; Cilia; Ciliopathies; Crystallization; Epistasis, Genetic; Gene Expression Regulation, Developmental; Homozygote; Mutation; Otolithic Membrane; Phenotype; Zebrafish; Zebrafish Proteins
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/251129
作者单位	Department of Biomedical Science, University of Sheffield, Sheffield, S10 2TN, United Kingdom; Department of Respiratory Sciences, University of Leicester, Leicester, LE1 7RH, United Kingdom
推荐引用方式 GB/T 7714	Leventea E.,Zhu Z.,Fang X.,et al. Ciliopathy genes are required for apical secretion of Cochlin, an otolith crystallization factor[J],2021,118(28).
APA	Leventea E..,Zhu Z..,Fang X..,Nikolaeva Y..,Markham E..,...&Malicki J.J..(2021).Ciliopathy genes are required for apical secretion of Cochlin, an otolith crystallization factor.Proceedings of the National Academy of Sciences of the United States of America,118(28).
MLA	Leventea E.,et al."Ciliopathy genes are required for apical secretion of Cochlin, an otolith crystallization factor".Proceedings of the National Academy of Sciences of the United States of America 118.28(2021).