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KIAA0319 influences cilia length, cell migration and mechanical cell-substrate interaction
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dc.contributor.author | Diaz, Rebeca | |
dc.contributor.author | Kronenberg, Nils Michael | |
dc.contributor.author | Martinelli, Angela | |
dc.contributor.author | Liehm, Philipp | |
dc.contributor.author | Riches, Andrew Clive | |
dc.contributor.author | Gather, Malte Christian | |
dc.contributor.author | Paracchini, Silvia | |
dc.date.accessioned | 2022-01-14T17:30:03Z | |
dc.date.available | 2022-01-14T17:30:03Z | |
dc.date.issued | 2022-01-14 | |
dc.identifier | 277126346 | |
dc.identifier | 34cbfa49-c5f6-4db3-8b0e-c40c710fd501 | |
dc.identifier | 000742753500015 | |
dc.identifier | 85123074871 | |
dc.identifier.citation | Diaz , 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/s41598-021-04539-3 | en |
dc.identifier.issn | 2045-2322 | |
dc.identifier.other | ORCID: /0000-0001-9934-8602/work/106397488 | |
dc.identifier.other | ORCID: /0000-0002-4857-5562/work/106397557 | |
dc.identifier.other | ORCID: /0000-0003-0937-5928/work/106397603 | |
dc.identifier.uri | https://hdl.handle.net/10023/24663 | |
dc.description | Funding: 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.abstract | Following 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.extent | 12 | |
dc.format.extent | 1923622 | |
dc.language.iso | eng | |
dc.relation.ispartof | Scientific Reports | en |
dc.subject | QH301 Biology | en |
dc.subject | QH426 Genetics | en |
dc.subject | RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry | en |
dc.subject | DAS | en |
dc.subject.lcc | QH301 | en |
dc.subject.lcc | QH426 | en |
dc.subject.lcc | RC0321 | en |
dc.title | KIAA0319 influences cilia length, cell migration and mechanical cell-substrate interaction | en |
dc.type | Journal article | en |
dc.contributor.sponsor | The Royal Society | en |
dc.contributor.sponsor | Carnegie Trust | en |
dc.contributor.sponsor | EPSRC | en |
dc.contributor.sponsor | BBSRC | en |
dc.contributor.sponsor | European Research Council | en |
dc.contributor.sponsor | The Wellcome Trust | en |
dc.contributor.institution | University of St Andrews. Cellular Medicine Division | en |
dc.contributor.institution | University of St Andrews. School of Medicine | en |
dc.contributor.institution | University of St Andrews. Sir James Mackenzie Institute for Early Diagnosis | en |
dc.contributor.institution | University of St Andrews. Centre for Biophotonics | en |
dc.contributor.institution | University of St Andrews. Biomedical Sciences Research Complex | en |
dc.contributor.institution | University of St Andrews. School of Physics and Astronomy | en |
dc.contributor.institution | University of St Andrews. St Andrews Bioinformatics Unit | en |
dc.identifier.doi | 10.1038/s41598-021-04539-3 | |
dc.description.status | Peer reviewed | en |
dc.identifier.grantnumber | RG160373 | en |
dc.identifier.grantnumber | 50341 | en |
dc.identifier.grantnumber | EP/P030017/1 | en |
dc.identifier.grantnumber | BB/P027148/1 | en |
dc.identifier.grantnumber | 640012 | en |
dc.identifier.grantnumber | 105621/Z/14/Z | en |
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