Biology subjects

Emery, G.

Publications and source records attributed to Emery, G..

6 recordsLinked to original sources

bioRxiv2025

An extended and apical supracellular actin network interconnects squamous carcinoma cells

Epithelial tissues form protective barriers while supporting critical functions such as absorption and secretion. Their structural and functional integrity relies on adherens junctions, which coordinate migration and transmit forces between adjacent cells by connecting their actin cytoskeleton. In this study, we report the presence of an apical supracellular actin network in squamous epithelial cells. Using squamous carcinoma A431 cells as a model, we characterized this network composed of star-shaped actin structures interconnected by linear actin bundles that span multiple cells. We demonstrate that the networks formation and maintenance require actomyosin contractility and intact adherens junctions, while tight junctions seem dispensable. Furthermore, this network dynamically reorganizes as cells migrate and preferentially aligns with the direction of movement. This contractile structure generates mechanical tension that extends across the apical surface of multiple cells. Our findings suggest that this supracellular actin network functions as a long-range force transmission device in squamous cells, advancing our understanding of the biomechanical properties of epithelia.

cell biology↗

bioRxiv2023

Dual regulation of Misshapen by Tao and Rap2l promotes collective cell migration

Collective cell migration occurs in various biological processes such as development, wound healing and metastasis. During Drosophila oogenesis, border cells (BC) form a cluster that migrates collectively inside the egg chamber. The Ste20-like kinase Misshapen (Msn) is a key regulator of BC migration coordinating the restriction of protrusion formation and contractile forces within the cluster. Here, we demonstrate that the kinase Tao acts as an upstream activator of Msn in BCs. Depletion of Tao significantly impedes BC migration and produces a phenotype similar to Msn loss-of-function. Furthermore, we show that the localization of Msn relies on its CNH domain, which interacts with the small GTPase Rap2l. Our findings indicate that Rap2l promotes the trafficking of Msn to the endolysosomal pathway. When Rap2l is depleted, the levels of Msn increase in the cytoplasm and at cell-cell junctions between BCs. Overall, our data suggest that Rap2l ensures that the levels of Msn are higher at the periphery of the cluster through the targeting of Msn to the degradative pathway. Together, we identified two distinct regulatory mechanisms that ensure the appropriate distribution and activation of Msn in BCs.

cell biology↗

bioRxiv2022

MAP4K4 regulates biomechanical forces at adherens junctions and focal adhesions to promote collective cell migration

Collective cell migration is important for normal development and tissue homeostasis, but can also promote cancer metastasis. To migrate collectively, cells need to coordinate their protrusion formation, rear retraction, adhesion sites dynamics, as well as forces generation and transmission. Nevertheless, the regulatory mechanisms coordinating these processes remain elusive. Using the A431 carcinoma cell line, we identify the kinase MAP4K4 as a central regulator of collective migration. We show that MAP4K4 inactivation blocks the migration of clusters while its overexpression decreases cluster cohesion. MAP4K4 regulates protrusion and retraction dynamics, remodels the actomyosin cytoskeleton, and controls the stability of both cell-cell and cell substrate adhesion. MAP4K4 promotes focal adhesion disassembly through the phosphorylation of Moesin, an actin and plasma membrane cross-linker, but disassembles adherens junctions through a Moesin-independent mechanism. By analyzing traction and intercellular forces, we found that the stabilization of adhesion sites in MAP4K4 loss of function leads to a tensional disequilibrium throughout the cell cluster, increasing the traction forces exerted onto the substrate and the tension loading at the cell-cell adhesions. Together, our results indicates that MAP4K4 activity is a key regulator of biomechanical forces at adhesion sites, promoting collective migration.

cell biology↗

bioRxiv2022

ArfGAP1 regulates the endosomal sorting of guidance receptors to promote directed collective cell migration in vivo

Chemotaxis drives diverse migrations important for development and involved in diseases, including cancer progression. Using border cells in the Drosophila egg chamber as a model for collective cell migration, we characterized the role of ArfGAP1 in regulating chemotaxis during this process. We found that ArfGAP1 is required for the maintenance of receptor tyrosine kinases, the guidance receptors, at the plasma membrane. In absence of ArfGAP1, the level of active receptors is reduced at the plasma membrane and increased in late endosomes. Consequently, clusters with impaired ArfGAP1 activity lose directionality. Furthermore, we found that the number and size of late endosomes and lysosomes are increased in the absence of ArfGAP1. Finally, genetic interactions suggest that ArfGAP1 acts on the kinase and GTPase Lrrk to regulate receptor sorting. Overall, our data indicate that ArfGAP1 is required to maintain the homeostasis of the endo-lysosomal pathway to ensure the maintenance of guidance receptors at the plasma membrane and promote chemotaxis.

cell biology↗

bioRxiv2020

Temporal coordination of collective migration and lumen formation by antagonism between two nuclear receptors

During development, cells often undergo multiple, distinct morphogenetic processes to form a tissue or organ, but how their temporal order and time interval are determined remain poorly understood. Here we show that the nuclear receptors E75 and DHR3 regulate the temporal order and time interval between the collective migration and lumen formation of a coherent group of about 8 cells called border cells during Drosophila oogenesis. In wild type egg chambers, border cells need to first collectively migrate to the anterior border of oocyte before undergoing lumen formation to form micropyle, the structure that is essential for sperm entry into the oocyte. We show that E75 is required for border cell migration and it antagonizes the activity of DHR3, which is necessary and sufficient for the subsequent lumen formation during micropyle formation. Furthermore, E75s loss of function or DHR3 overexpression each leads to precocious lumen formation before collective migration, an incorrect temporal order for the two morphogenetic processes. Interestingly, both E75 and DHR3s levels are simultaneously elevated in response to signaling from the EcR, a steroid hormone receptor that initiates border cell migration. Subsequently, the decrease of E75 levels in response to decreased EcR signaling leads to the de-repression of DHR3s activity and hence switch-on of lumen formation, contributing to the regulation of time interval between collective migration and micropyle formation.

developmental biology↗

bioRxiv2019

Quantitative proteomics identifies novel PIAS1 protein substrates involved in cell migration and motility

The Protein Inhibitor of Activated STAT 1 (PIAS1) is an E3 SUMO ligase that plays important roles in various cellular pathways, including STAT signaling, p53 pathway, and the steroid hormone signaling pathway. PIAS1 can SUMOylate PML (at Lys-65 and Lys-160) and PML-RAR promoting their ubiquitin-mediated degradation. Increasing evidence shows that PIAS1 is overexpressed in various human malignancies, including prostate and lung cancers. To understand the mechanism of action of PIAS1, we developed a quantitative SUMO proteomic approach to identify potential substrates of PIAS1 in a system-wide manner. Our analyses enabled the profiling of 983 SUMO sites on 544 proteins, of which 204 SUMO sites on 123 proteins were identified as putative PIAS1 substrates. These substrates are involved in different cellular processes, such as transcriptional regulation, DNA binding and cytoskeleton dynamics. Further functional studies on Vimentin (VIM), a type III intermediate filament protein involved in cytoskeleton organization and cell motility, revealed that PIAS1 exerts its effects on cell migration and cell invasion through the SUMOylation of VIM at Lys-439 and Lys-445 residues. VIM SUMOylation was necessary for its dynamic disassembly, and cells expressing a non-SUMOylatable VIM mutant showed reduced levels of proliferation and migration. Our approach not only provides a novel strategy for the identification of E3 SUMO ligase substrates, but also yields valuable biological insights into the unsuspected role of PIAS1 and VIM SUMOylation on cell motility.

cancer biology↗