RBL2 represses the transcriptional activity of Multicilin to inhibit multiciliogenesis

Erik J. Quiroz; Seongjae Kim; Lalit K. Gautam; Zea Borok; Christopher Kintner; Amy L. Ryan

doi:10.1101/2023.08.04.551992

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RBL2 represses the transcriptional activity of Multicilin to inhibit multiciliogenesis

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RBL2 represses the transcriptional activity of Multicilin to inhibit multiciliogenesis

Erik J. Quiroz, Seongjae Kim, Lalit K. Gautam, Zea Borok, Christopher Kintner and Amy L. Ryan

bioRxiv

Cold Spring Harbor Laboratory

08/04/2023

DOI: 10.1101/2023.08.04.551992

PMCID: PMC10418160

PMID: 37577572

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https://doi.org/10.1101/2023.08.04.551992View

Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

A core pathophysiologic feature underlying many respiratory diseases is multiciliated cell dysfunction, leading to inadequate mucociliary clearance. Due to the prevalence and highly variable etiology of mucociliary dysfunction in respiratory diseases, it is critical to understand the mechanisms controlling multiciliogenesis that may be targeted to restore functional mucociliary clearance. Multicilin, in a complex with E2F4, is necessary and sufficient to drive multiciliogenesis in airway epithelia, however this does not apply to all cell types, nor does it occur evenly across all cells in the same cell population. In this study we further investigated how co-factors regulate the ability of Multicilin to drive multiciliogenesis. Combining data in mouse embryonic fibroblasts and human bronchial epithelial cells, we identify RBL2 as a repressor of the transcriptional activity of Multicilin. Knockdown of RBL2 in submerged cultures or phosphorylation of RBL2 in response to apical air exposure, in the presence of Multicilin, allows multiciliogenesis to progress. These data demonstrate a dynamic interaction between RBL2 and Multicilin that regulates the capacity of cells to differentiate and multiciliate. Identification of this mechanism has important implications for facilitating MCC differentiation in diseases with impaired mucociliary clearance.

Details

Title: Subtitle: RBL2 represses the transcriptional activity of Multicilin to inhibit multiciliogenesis
Creators: Erik J. Quiroz - University of Iowa
Seongjae Kim - University of California San Diego
Lalit K. Gautam - University of Iowa
Zea Borok - University of California San Diego
Christopher Kintner
Amy L. Ryan - University of Iowa
Resource Type: Preprint
Publication Details: bioRxiv
DOI: 10.1101/2023.08.04.551992
PMID: 37577572
PMCID: PMC10418160
Publisher: Cold Spring Harbor Laboratory
Language: English
Date posted: 08/04/2023
Academic Unit: Anatomy and Cell Biology
Record Identifier: 9984455360302771

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