KIAA0319 influences cilia length, cell migration and mechanical cell-substrate interaction.

Autor: Diaz R; School of Medicine, University of St Andrews, St Andrews, KY16 9TF, UK., Kronenberg NM; SUPA, School of Physics and Astronomy, University of St Andrews, St Andrews, KY16 9SS, UK.; Department of Chemistry, Humboldt Centre for Nano- and Biophotonics, University of Cologne, 50939, Cologne, Germany., Martinelli A; School of Medicine, University of St Andrews, St Andrews, KY16 9TF, UK., Liehm P; SUPA, School of Physics and Astronomy, University of St Andrews, St Andrews, KY16 9SS, UK., Riches AC; School of Medicine, University of St Andrews, St Andrews, KY16 9TF, UK., Gather MC; SUPA, School of Physics and Astronomy, University of St Andrews, St Andrews, KY16 9SS, UK. mcg6@st-andrews.ac.uk.; Department of Chemistry, Humboldt Centre for Nano- and Biophotonics, University of Cologne, 50939, Cologne, Germany. mcg6@st-andrews.ac.uk., Paracchini S; School of Medicine, University of St Andrews, St Andrews, KY16 9TF, UK. sp58@st-andrews.ac.uk.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2022 Jan 14; Vol. 12 (1), pp. 722. Date of Electronic Publication: 2022 Jan 14.
DOI: 10.1038/s41598-021-04539-3
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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