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

Rebeca Diaz; Nils Michael Kronenberg; Angela Martinelli; Philipp Liehm; Andrew Clive Riches; Malte Christian Gather; Silvia Paracchini

doi:10.1038/s41598-021-04539-3

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

Rebeca Diaz, Nils Michael Kronenberg, Angela Martinelli, Philipp Liehm, Andrew Clive Riches, Malte Christian Gather^*, Silvia Paracchini^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	722
Number of pages	12
Journal	Scientific Reports
Volume	12
DOIs	https://doi.org/10.1038/s41598-021-04539-3
Publication status	Published - 14 Jan 2022

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6 Finished

Resonant and shaped photonics for under: Resonant and shaped photonics for understanding the physical and biomedical world
Dholakia, K. (PI) & Gather, M. C. (CoI)
1/08/17 → 31/07/22
Project: Standard
Interference Traction Force Microscopy: Interference Traction Force Microscopy (iTFM) for Bioimaging of Cellular Forces
Gather, M. C. (PI)
BBSRC
1/07/17 → 30/09/18
Project: Standard
Silvia Paracchini: KIAA0319: a molecular window to understand the link between dyslexia and asymmetries
Paracchini, S. (PI)
Carnegie Trust
1/10/16 → 31/03/18
Project: Standard

The dyslexia susceptibility gene KIAA0319 influences cilia length, cell migration and mechanical cell-substrate interaction (dataset)
Diaz Vazquez, R. (Creator), Kronenberg, N. M. (Creator), Martinelli, A. (Creator), Liehm, P. (Creator), Riches, A. C. (Creator), Gather, M. C. (Creator) & Paracchini, S. (Creator), University of St Andrews, 2022
DOI: 10.17630/3eb826ac-eea7-478e-b6df-ee4dd50a96fd
Dataset

File

1 Article

The dyslexia susceptibility gene KIAA0319 influences cilia length, cell migration and mechanical cell-substrate interaction
Paracchini, S., 2019, In: biorxiv.
Research output: Contribution to journal › Article

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Cite this

@article{34cbfa49c5f64db38b0ec40c710fd501,

title = "KIAA0319 influences cilia length, cell migration and mechanical cell-substrate interaction",

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.",

author = "Rebeca Diaz and Kronenberg, {Nils Michael} and Angela Martinelli and Philipp Liehm and Riches, {Andrew Clive} and Gather, {Malte Christian} and Silvia Paracchini",

note = "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.",

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journal = "Scientific Reports",

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AU - Diaz, Rebeca

AU - Kronenberg, Nils Michael

AU - Martinelli, Angela

AU - Liehm, Philipp

AU - Riches, Andrew Clive

AU - Gather, Malte Christian

AU - Paracchini, Silvia

N1 - 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.

PY - 2022/1/14

Y1 - 2022/1/14

N2 - 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.

AB - 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.

U2 - 10.1038/s41598-021-04539-3

DO - 10.1038/s41598-021-04539-3

M3 - Article

SN - 2045-2322

VL - 12

JO - Scientific Reports

JF - Scientific Reports

M1 - 722

ER -

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

Abstract

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Projects

Resonant and shaped photonics for under: Resonant and shaped photonics for understanding the physical and biomedical world

Interference Traction Force Microscopy: Interference Traction Force Microscopy (iTFM) for Bioimaging of Cellular Forces

Silvia Paracchini: KIAA0319: a molecular window to understand the link between dyslexia and asymmetries

Datasets

The dyslexia susceptibility gene KIAA0319 influences cilia length, cell migration and mechanical cell-substrate interaction (dataset)

Research output

The dyslexia susceptibility gene KIAA0319 influences cilia length, cell migration and mechanical cell-substrate interaction

Cite this