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J Cell Sci. 2018 Feb 8;131(3). pii: jcs209361. doi: 10.1242/jcs.209361.

EFA6 proteins regulate lumen formation through α-actinin 1.

Author information

1
Université Côte d'Azur, CNRS, Institut de Pharmacologie Moléculaire et Cellulaire (IPMC), Valbonne, F-06560, France.
2
Centre de Recherche en Cancérologie de Marseille (CRCM), 'Cell Polarity, Cell Signalling and Cancer', Equipe Labellisée Ligue Contre le Cancer, Inserm U1068, Marseille, F-13009, France; CNRS, UMR7258, Marseille, F-13009, France; Institut Paoli-Calmettes, Marseille, F-13009, France; Aix-Marseille University, UM105, Marseille, F-13284, France.
3
Université Côte d'Azur, CNRS, Institut de Pharmacologie Moléculaire et Cellulaire (IPMC), Valbonne, F-06560, France luton@ipmc.cnrs.fr.

Abstract

A key step of epithelial morphogenesis is the creation of the lumen. Luminogenesis by hollowing proceeds through the fusion of apical vesicles at cell-cell contacts. The small nascent lumens grow through extension, coalescence and enlargement, coordinated with cell division, to give rise to a single central lumen. Here, by using MDCK cells grown in 3D-culture, we show that EFA6A (also known as PSD) participates in luminogenesis. EFA6A recruits α-actinin 1 (ACTN1) through direct binding. In polarized cells, ACTN1 was found to be enriched at the tight junction where it acts as a primary effector of EFA6A for normal luminogenesis. Both proteins are essential for the lumen extension and enlargement, where they mediate their effect by regulating the cortical acto-myosin contractility. Finally, ACTN1 was also found to act as an effector for the isoform EFA6B (also known as PSD4) in the human mammary tumoral MCF7 cell line. EFA6B restored the glandular morphology of this tumoral cell line in an ACTN1-dependent manner. Thus, we identified new regulators of cyst luminogenesis essential for the proper maturation of a newly-formed lumen into a single central lumen.

KEYWORDS:

ACTN1; Contractility; EFA6; Epithelium; Lumen

PMID:
29246944
DOI:
10.1242/jcs.209361
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Conflict of interest statement

Competing interestsThe authors declare no competing or financial interests.

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