Paracingulin recruits CAMSAP3 to tight junctions and regulates microtubule and polarized epithelial cell organization.


Journal

Journal of cell science
ISSN: 1477-9137
Titre abrégé: J Cell Sci
Pays: England
ID NLM: 0052457

Informations de publication

Date de publication:
01 03 2024
Historique:
received: 25 10 2022
accepted: 17 03 2023
medline: 17 5 2023
pubmed: 5 4 2023
entrez: 4 4 2023
Statut: ppublish

Résumé

Paracingulin (CGNL1) is recruited to tight junctions (TJs) by ZO-1 and to adherens junctions (AJs) by PLEKHA7. PLEKHA7 has been reported to bind to the microtubule minus-end-binding protein CAMSAP3, to tether microtubules to the AJs. Here, we show that knockout (KO) of CGNL1, but not of PLEKHA7, results in the loss of junctional CAMSAP3 and its redistribution into a cytoplasmic pool both in cultured epithelial cells in vitro and mouse intestinal epithelium in vivo. In agreement, GST pulldown analyses show that CGNL1, but not PLEKHA7, interacts strongly with CAMSAP3, and the interaction is mediated by their respective coiled-coil regions. Ultrastructure expansion microscopy shows that CAMSAP3-capped microtubules are tethered to junctions by the ZO-1-associated pool of CGNL1. The KO of CGNL1 results in disorganized cytoplasmic microtubules and irregular nuclei alignment in mouse intestinal epithelial cells, altered cyst morphogenesis in cultured kidney epithelial cells, and disrupted planar apical microtubules in mammary epithelial cells. Together, these results uncover new functions of CGNL1 in recruiting CAMSAP3 to junctions and regulating microtubule cytoskeleton organization and epithelial cell architecture.

Identifiants

pubmed: 37013686
pii: 306237
doi: 10.1242/jcs.260745
pmc: PMC10184829
pii:
doi:

Substances chimiques

Camsap3 protein, mouse 0
Cytoskeletal Proteins 0
Microtubule-Associated Proteins 0
Cgnl1 protein, mouse 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Swiss National Science Foundation
ID : 31003A_135730
Pays : Switzerland

Informations de copyright

© 2023. Published by The Company of Biologists Ltd.

Déclaration de conflit d'intérêts

Competing interests The authors declare no competing or financial interests.

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Auteurs

Arielle Flinois (A)

Department of Molecular and Cellular Biology, Faculty of Sciences, University of Geneva, 1205 Geneva, Switzerland.

Isabelle Méan (I)

Department of Molecular and Cellular Biology, Faculty of Sciences, University of Geneva, 1205 Geneva, Switzerland.

Annick Mutero-Maeda (A)

Department of Molecular and Cellular Biology, Faculty of Sciences, University of Geneva, 1205 Geneva, Switzerland.

Laurent Guillemot (L)

Department of Molecular and Cellular Biology, Faculty of Sciences, University of Geneva, 1205 Geneva, Switzerland.

Sandra Citi (S)

Department of Molecular and Cellular Biology, Faculty of Sciences, University of Geneva, 1205 Geneva, Switzerland.

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Classifications MeSH