Open AccessEFA6 regulates lumen formation through alpha-actinin 1
Author(s) -
Julie Milanini,
Racha Fayad,
Mariagrazia Partisani,
Patrick Lécine,
Jean-Paul Borg,
Michel Franco,
Frédéric Luton
Publication year - 2017
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.209361
Subject(s) - biology , microbiology and biotechnology , lumen (anatomy) , morphogenesis , effector , cell division , myosin , vesicle , cell , biochemistry , membrane , gene
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 contact. The small nascent lumens grow through extension, coalescence and enlargement coordinated with cell division to give rise to a single central lumen. Here, using MDCK cells grown in 3D-culture, we show that EFA6A 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 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.