KIAA0319 influences cilia length, cell migration and mechanical cell-substrate interaction
Date
14/01/2022Author
Grant ID
RG160373
50341
EP/P030017/1
BB/P027148/1
640012
105621/Z/14/Z
Keywords
Metadata
Show full item recordAbstract
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.
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
Publication
Scientific Reports
Status
Peer reviewed
ISSN
2045-2322Type
Journal article
Rights
Copyright © 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/.
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.Collections
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