How adherens junctions move cells during collective migration

Gupta, Shafali; Yap, Alpha

doi:10.12703/r/10-56

Cited by 12 publications

(14 citation statements)

References 51 publications

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“…Apical junctions are critical not only for the establishment of epithelial barriers, but also for the repair of injured cell monolayers, by controlling collective migration of epithelial cells. 2 , 3 Given the observed role of UNC-45A in regulating junctional integrity, we sought to examine if this chaperone also influences on IEC motility. Loss of UNC-45A significantly delayed collective migration of HT-29cf8 and SK-CO15 cell monolayers in a wound healing assay ( Figure 5A - D ).…”

Section: Resultsmentioning

confidence: 99%

“…Formation of intercellular junctions represents a key molecular event that is required for epithelial cell differentiation, apico‐basal polarization and establishment of the paracellular barrier 1 . It is also essential for tissue morphogenesis by enabling the orchestrated movement, expansion and folding of epithelial sheets 2,3 . Although cell–cell engagement results in the assembly of several adhesive structures, the apically located tight junctions (TJ) and adherens junctions (AJ) are arguably the most important regulators of epithelial barriers and homeostasis 4–7 …”

Section: Introductionmentioning

confidence: 99%

“…1 It is also essential for tissue morphogenesis by enabling the orchestrated movement, expansion and folding of epithelial sheets. 2,3 Although cell-cell engagement results in the assembly of several adhesive structures, the apically located tight junctions (TJ) and adherens junctions (AJ) are arguably the most important regulators of epithelial barriers and homeostasis. [4][5][6][7] TJ and AJ are elaborate multiprotein complexes that include transmembrane adhesive proteins connected to various intracellular scaffolds.…”

Section: Introductionmentioning

confidence: 99%

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A myosin chaperone, UNC‐45A, is a novel regulator of intestinal epithelial barrier integrity and repair

et al. 2022

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The actomyosin cytoskeleton serves as a key regulator of the integrity and remodeling of epithelial barriers by controlling assembly and functions of intercellular junctions and cell‐matrix adhesions. Although biochemical mechanisms that regulate the activity of non‐muscle myosin II (NM‐II) in epithelial cells have been extensively investigated, little is known about assembly of the contractile myosin structures at the epithelial adhesion sites. UNC‐45A is a cytoskeletal chaperone that is essential for proper folding of NM‐II heavy chains and myofilament assembly. We found abundant expression of UNC‐45A in human intestinal epithelial cell (IEC) lines and in the epithelial layer of the normal human colon. Interestingly, protein level of UNC‐45A was decreased in colonic epithelium of patients with ulcerative colitis. CRISPR/Cas9‐mediated knock‐out of UNC‐45A in HT‐29cf8 and SK‐CO15 IEC disrupted epithelial barrier integrity, impaired assembly of epithelial adherence and tight junctions and attenuated cell migration. Consistently, decreased UNC‐45 expression increased permeability of the Drosophila gut in vivo. The mechanisms underlying barrier disruptive and anti‐migratory effects of UNC‐45A depletion involved disorganization of the actomyosin bundles at epithelial junctions and the migrating cell edge. Loss of UNC‐45A also decreased contractile forces at apical junctions and matrix adhesions. Expression of deletion mutants revealed roles for the myosin binding domain of UNC‐45A in controlling IEC junctions and motility. Our findings uncover a novel mechanism that regulates integrity and restitution of the intestinal epithelial barrier, which may be impaired during mucosal inflammation.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A myosin chaperone, UNC‐45A, is a novel regulator of intestinal epithelial barrier integrity and repair

et al. 2022

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“…The prerequisite of cell movement is the formation of leading-edge protrusions. Gupta and Yap (2021) revealed different ways by which adherens junctions promote the locomotion of cells within tissues: through protrusions and contraction of the junctions. Small G proteins of the Rho family regulate cell movement by promoting protrusion and stimulating adhesion (Etienne-Manneville, 2013).…”

Section: Introductionmentioning

confidence: 99%

Surface activity of cancer cells: The fusion of two cell aggregates

Pajić‐Lijaković¹,

Milivojević²

2023

Biocell

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A key feature that distinguishes cancer cells from all other cells is their capability to spread throughout the body.Although how cancer cells collectively migrate by following molecular rules which influence the state of cell-cell adhesion contacts has been comprehensively formulated, the impact of physical interactions on cell spreading remains less understood. Cumulative effects of physical interactions exist as the interplay between various physical parameters such as (1) tissue surface tension, (2) viscoelasticity caused by collective cell migration, and (3) solid stress accumulated in the cell aggregate core region. This review aims to point out the role of these physical parameters in cancer cell spreading by considering and comparing the rearrangement of various mono-cultured cancer and epithelial model systems such as the fusion of two cell aggregates. While epithelial cells undergo volumetric cell rearrangement driven by the tissue surface tension, which directs cell movement from the surface to the core region of two-aggregate systems, cancer cells rather perform surface cell rearrangement. Cancer cells migrate toward the surface of the two-aggregate system driven by the solid stress while the surface tension is significantly reduced. The solid stress, accumulated in the core region of the two-aggregate system, is capable of suppressing the movement of epithelial cells that can undergo the jamming state transition; however, this stress enhances the movement of cancer cells. We have focused here on the multi-scale rheological modeling approaches that aimed at reproducing and understanding these biological systems.

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“…Another member of the classical cadherin family is Neural cadherin (N-cad, CDH2), a 135 kDa transmembrane protein first identified as a neural cells adhesion molecule, although later was found to be expressed in several tissues [ 19 ]. Participation of E-cad and N-cad in cell-cell adhesion and signal transduction events has been extensively investigated in embryonic and somatic cells in health and disease [ 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. While its structure resembles that of E-cad, N-cad mediates homotypic binding, although during tumor progression it also participates in heterotypic adhesion events involving E-cad on the cancer cell membrane and N-cad on the fibroblast membrane [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

Epithelial and Neural Cadherin in Mammalian Fertilization: Studies in the Mouse Model

Verón

Veiga

Cameo³

et al. 2021

Cells

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Successful mammalian fertilization requires a well-orchestrated sequence of molecular events leading to gamete fusion. Since this interaction involves Ca2+-dependent adhesion events, the participation of the Ca+2-dependent cell-cell adhesion proteins Epithelial (E-cad) and Neural (N-cad) cadherin is envisaged. We have previously reported the expression of E-cad and N-cad in human gametes and showed evidence of their involvement in sperm-oocyte adhesion events leading to fertilization. To overcome ethical limitations associated with the use of human gametes in fertilization-related studies, the mouse has been selected worldwide as the experimental model for over 4 decades. Herein, we report a detailed study aimed at characterizing the expression of E-cad and N-cad in murine gametes and their involvement in murine fertilization using specific antibodies and blocking peptides towards both adhesion proteins. E-cad and N-cad protein forms, as well as other members of the adhesion complex, specifically β-catenin and actin, were identified in spermatozoa, cumulus cells and oocytes protein extracts by means of Western immunoblotting. In addition, subcellular localization of these proteins was determined in whole cells using optical fluorescent microscopy. Gamete pre-incubation with anti-E-cad (ECCD-1) or N-cad (H-63) antibodies resulted in decreased (p < 0.05) In Vitro Fertilization (IVF) rates, when using both cumulus-oocytes complexes and cumulus-free oocytes. Moreover, IVF assays done with denuded oocytes and either antibodies or blocking peptides against E-cad and N-cad led to lower (p < 0.05) fertilization rates. When assessing each step, penetration of the cumulus mass was lower (p < 0.05) when spermatozoa were pre-incubated with ECCD-1 or blocking peptides towards E-cad or towards both E- and N-cad. Moreover, sperm-oolemma binding was impaired (p < 0.0005) after sperm pre-incubation with E-cad antibody or blocking peptide towards E-cad, N-cad or both proteins. Finally, sperm-oocyte fusion was lower (p < 0.05) after sperm pre-incubation with either antibody or blocking peptide against E-cad or N-cad. Our studies demonstrate the expression of members of the adherent complex in the murine model, and the use of antibodies and specific peptides revealed E-cad and N-cad participation in mammalian fertilization.

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How adherens junctions move cells during collective migration

Cited by 12 publications

References 51 publications

A myosin chaperone, UNC‐45A, is a novel regulator of intestinal epithelial barrier integrity and repair

A myosin chaperone, UNC‐45A, is a novel regulator of intestinal epithelial barrier integrity and repair

Surface activity of cancer cells: The fusion of two cell aggregates

Epithelial and Neural Cadherin in Mammalian Fertilization: Studies in the Mouse Model

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