EFA6 proteins regulate lumen formation through α-actinin 1

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.

Host intestinal biomarker identification in a gut leakage model in broilers

“…Epithelial damage has been shown to be associated with altered protein expression and distribution of intercellular connections, including tight junctions [44]. Alpha-actinin-4 (ACTN4), found to be more abundant in intestinal content in the challenge group as compared to the control group, was shown to be localized in the apical part of chicken intestinal epithelial cells [45], more specifically as a component of the tight junction ( zonula occludens ) [46] and/or belt desmosomes ( zonula adherens ) [47]. Changes in gut permeability induced by enteric pathogens and/or parasites can also be the consequence of damage to these tight junctions [48].…”

Insane in the apical membrane: Trafficking events mediating apicobasal epithelial polarity during tube morphogenesis

“…During the early 2–4 cell stages, EFA6 likely acts as a GEF to activate Arf6, which is known to function in apical trafficking 47 and tubulogenesis 48 . Then, once a nascent lumen has formed, EFA6 interacts with alpha-actinin 1 which modulates actomyosin contractility to help lumen coalescence and enlargement 49 . Finally, while Podocalyxin is a commonly used apical membrane marker, it may play a more active role in lumenogenesis.…”

Identification of GSN and LAMC2 as Key Prognostic Genes of Bladder Cancer by Integrated Bioinformatics Analysis

“…The function of PSD4 was related to driving the cell line into epithelial-to-mesenchymal transition. In human breast tumors, the reduced expression of PSD4 was associated with increasing the poor prognosis and cancer stemness [ 37 , 38 ]. In the transitional cell carcinoma lymphatic metastasis, we identified HIPK2 and SEH1 like nucleoporin (SEH1L).…”