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dc.contributor.authorDiaz, Rebeca
dc.contributor.authorKronenberg, Nils Michael
dc.contributor.authorMartinelli, Angela
dc.contributor.authorLiehm, Philipp
dc.contributor.authorRiches, Andrew Clive
dc.contributor.authorGather, Malte Christian
dc.contributor.authorParacchini, Silvia
dc.date.accessioned2022-01-14T17:30:03Z
dc.date.available2022-01-14T17:30:03Z
dc.date.issued2022-01-14
dc.identifier.citationDiaz , R , Kronenberg , N M , Martinelli , A , Liehm , P , Riches , A C , Gather , M C & Paracchini , S 2022 , ' KIAA0319 influences cilia length, cell migration and mechanical cell-substrate interaction ' , Scientific Reports , vol. 12 , 722 . https://doi.org/10.1038/s41598-021-04539-3en
dc.identifier.issn2045-2322
dc.identifier.otherPURE: 277126346
dc.identifier.otherPURE UUID: 34cbfa49-c5f6-4db3-8b0e-c40c710fd501
dc.identifier.otherORCID: /0000-0001-9934-8602/work/106397488
dc.identifier.otherORCID: /0000-0002-4857-5562/work/106397557
dc.identifier.otherORCID: /0000-0003-0937-5928/work/106397603
dc.identifier.urihttp://hdl.handle.net/10023/24663
dc.descriptionFunding: This work was supported by Action Medical Research/ The Chief Scientist (CSO) Office, Scotland [GN 2614], Royal Society [RG160373], Carnegie Trust [50341], Wellcome Trust ISSF grant 105621/Z/14/Z, and RS Macdonald Charitable Trust grants to SP and Engineering and Physical Sciences Research Council [EP/P030017/1], Biotechnology and Biological Sciences Research Council [BB/P027148/1], and the European Research Council Starting Grant ABLASE [640012] grants to MCG. SP is a Royal Society University Research Fellow.en
dc.description.abstractFollowing its association with dyslexia in multiple genetic studies, the KIAA0319 gene has been extensively investigated in different animal models but its function in neurodevelopment remains poorly understood. We developed the first human cellular knockout model for KIAA0319 in RPE1 retinal pigment epithelia cells via CRISPR-Cas9n to investigate its role in processes suggested but not confirmed in previous studies, including cilia formation and cell migration. We observed in the KIAA0319 knockout increased cilia length and accelerated cell migration. Using Elastic Resonator Interference Stress Microscopy (ERISM), we detected an increase in cellular force for the knockout cells that was restored by a rescue experiment. Combining ERISM and immunostaining we show that RPE1 cells exert highly dynamic, piconewton vertical pushing forces through actin-rich protrusions that are surrounded by vinculin-rich pulling sites. This protein arrangement and force pattern has previously been associated to podosomes in other cells. KIAA0319 depletion reduces the fraction of cells forming these actin-rich protrusions. Our results suggest an involvement of KIAA0319 in cilia biology and cell–substrate force regulation.
dc.format.extent12
dc.language.isoeng
dc.relation.ispartofScientific Reportsen
dc.rightsCopyright © The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.en
dc.subjectQH301 Biologyen
dc.subjectQH426 Geneticsen
dc.subjectRC0321 Neuroscience. Biological psychiatry. Neuropsychiatryen
dc.subjectDASen
dc.subject.lccQH301en
dc.subject.lccQH426en
dc.subject.lccRC0321en
dc.titleKIAA0319 influences cilia length, cell migration and mechanical cell-substrate interactionen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.Cellular Medicine Divisionen
dc.contributor.institutionUniversity of St Andrews.School of Medicineen
dc.contributor.institutionUniversity of St Andrews.Sir James Mackenzie Institute for Early Diagnosisen
dc.contributor.institutionUniversity of St Andrews.Centre for Biophotonicsen
dc.contributor.institutionUniversity of St Andrews.Biomedical Sciences Research Complexen
dc.contributor.institutionUniversity of St Andrews.School of Physics and Astronomyen
dc.contributor.institutionUniversity of St Andrews.St Andrews Bioinformatics Uniten
dc.identifier.doihttps://doi.org/10.1038/s41598-021-04539-3
dc.description.statusPeer revieweden


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