Universität zu Köln

Diaz, Rebeca, Kronenberg, Nils M., Martinelli, Angela ORCID: 0000-0001-6442-3190, Liehm, Philipp, Riches, Andrew C., Gather, Malte C. and Paracchini, Silvia ORCID: 0000-0001-9934-8602 (2022). KIAA0319 influences cilia length, cell migration and mechanical cell-substrate interaction. Sci Rep, 12 (1). BERLIN: NATURE PORTFOLIO. ISSN 2045-2322

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Diaz, Rebeca UNSPECIFIED UNSPECIFIED UNSPECIFIED Kronenberg, Nils M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Martinelli, Angela UNSPECIFIED orcid.org/0000-0001-6442-3190 UNSPECIFIED Liehm, Philipp UNSPECIFIED UNSPECIFIED UNSPECIFIED Riches, Andrew C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gather, Malte C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Paracchini, Silvia UNSPECIFIED orcid.org/0000-0001-9934-8602 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-668542
DOI:	10.1038/s41598-021-04539-3
Journal or Publication Title:	Sci Rep
Volume:	12
Number:	1
Date:	2022
Publisher:	NATURE PORTFOLIO
Place of Publication:	BERLIN
ISSN:	2045-2322
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DYSLEXIA; GENE; PRECISION; TENSION; FORCES; DNA Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/66854