Gutenberg Open Science: SANS (USH1G) molecularly links the human Usher syndrome protein network to the intraflagellar transport module by direct binding to IFT-B proteins

Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-5260

Full metadata record

DC Field	Value	Language
dc.contributor.author	Sorusch, Nasrin	-
dc.contributor.author	Yildirim, Adem	-
dc.contributor.author	Knapp, Barbara	-
dc.contributor.author	Janson, Julia	-
dc.contributor.author	Fleck, Wiebke	-
dc.contributor.author	Scharf, Caroline	-
dc.contributor.author	Wolfrum, Uwe	-
dc.date.accessioned	2020-10-27T08:30:22Z	-
dc.date.available	2020-10-27T08:30:22Z	-
dc.date.issued	2019	-
dc.identifier.uri	https://openscience.ub.uni-mainz.de/handle/20.500.12030/5264	-
dc.description.abstract	The human Usher syndrome (USH) is a retinal ciliopathy, characterized by profound congenital deafness, variable vestibular dysfunction and pre-pubertal onset of retinitis pigmentosa. In the effected sensory cells, USH protein networks are assumed to function in ciliary transport processes. The USH1G protein SANS is a scaffold of the ciliary/periciliary USH protein network of photoreceptor cells. Moreover, SANS is associated with microtubules, the transport routes for protein delivery toward the cilium. To enlighten the role of SANS in ciliary transport processes, we aimed to identify transport related proteins associated with SANS. The intraflagellar transport (IFT) system is a conserved mechanism for bi-directional transport toward and through primary cilia. Thus, we tested the direct binding of SANS to IFT molecules, namely IFT20, IFT57, and IFT74 in 1:1 yeast-two-hybrid assay. The identified SANS-IFT interactions were validated in vitro via independent complementary interaction assays and in cells by applying membrane targeting assays. Quantitative immunofluorescence microscopy revealed the co-localization of SANS with IFT20, IFT52, and IFT57 particularly at ciliary base of wild type mouse photoreceptor cells. Analysis of photoreceptor cells of SANS knock out mice revealed the decrease of IFTs in the ciliary compartment indicating a role of SANS in the proper positioning of IFT-B molecules in primary cilia. Our study demonstrated direct binding of IFT complex B proteins IFT52 and IFT57 to the N-terminal ankyrin repeats and the central domain of SANS. Our data also indicate that pathologic mutations in the N-terminus of SANS lead to the loos of SANS binding to IFT-B molecules. Our findings provide direct evidence for a molecular link between the ciliary USH protein network and the IFT transport module in primary cilia.	en_GB
dc.description.sponsorship	DFG, Open Access-Publizieren Universität Mainz / Universitätsmedizin Mainz	de
dc.language.iso	eng	de
dc.rights	CC BY	*
dc.rights.uri	https://creativecommons.org/licenses/by/4.0/	*
dc.subject.ddc	570 Biowissenschaften	de_DE
dc.subject.ddc	570 Life sciences	en_GB
dc.title	SANS (USH1G) molecularly links the human Usher syndrome protein network to the intraflagellar transport module by direct binding to IFT-B proteins	en_GB
dc.type	Zeitschriftenaufsatz	de
dc.identifier.doi	http://doi.org/10.25358/openscience-5260	-
jgu.type.dinitype	article	en_GB
jgu.type.version	Published version	de
jgu.type.resource	Text	de
jgu.organisation.department	FB 10 Biologie	de
jgu.organisation.number	7970	-
jgu.organisation.name	Johannes Gutenberg-Universität Mainz	-
jgu.rights.accessrights	openAccess	-
jgu.journal.title	Frontiers in cell and developmental biology	de
jgu.journal.volume	7	de
jgu.pages.alternative	Art. 216	de
jgu.publisher.year	2019	-
jgu.publisher.name	Frontiers Media	de
jgu.publisher.place	Lausanne	de
jgu.publisher.uri	https://doi.org/10.3389/fcell.2019.00216	de
jgu.publisher.issn	2296-634X	de
jgu.organisation.place	Mainz	-
jgu.subject.ddccode	570	de
jgu.publisher.doi	10.3389/fcell.2019.00216
jgu.organisation.ror	https://ror.org/023b0x485
Appears in collections:	JGU-Publikationen

Files in This Item:

	File	Description	Size	Format
	sorusch_nasrin-sans_(ush1g)_m-20201027092115642.pdf		4.02 MB	Adobe PDF	View/Open

Show simple item record