scholarly journals The force-sensitive protein Ajuba regulates cell adhesion during epithelial morphogenesis

2018 ◽  
Vol 217 (10) ◽  
pp. 3715-3730 ◽  
Author(s):  
William Razzell ◽  
Maria E. Bustillo ◽  
Jennifer A. Zallen
Keyword(s):  
Cell Adhesion ◽  
Adherens Junctions ◽  
The Body ◽  
Epithelial Morphogenesis ◽  
Mechanical Forces ◽  
Lim Domain ◽  
Lim Domains ◽  
High Tension ◽  
Axis Elongation ◽  
Epithelial Sheets

The reorganization of cells in response to mechanical forces converts simple epithelial sheets into complex tissues of various shapes and dimensions. Epithelial integrity is maintained throughout tissue remodeling, but the mechanisms that regulate dynamic changes in cell adhesion under tension are not well understood. In Drosophila melanogaster, planar polarized actomyosin forces direct spatially organized cell rearrangements that elongate the body axis. We show that the LIM-domain protein Ajuba is recruited to adherens junctions in a tension-dependent fashion during axis elongation. Ajuba localizes to sites of myosin accumulation at adherens junctions within seconds, and the force-sensitive localization of Ajuba requires its N-terminal domain and two of its three LIM domains. We demonstrate that Ajuba stabilizes adherens junctions in regions of high tension during axis elongation, and that Ajuba activity is required to maintain cell adhesion during cell rearrangement and epithelial closure. These results demonstrate that Ajuba plays an essential role in regulating cell adhesion in response to mechanical forces generated by epithelial morphogenesis.

scholarly journals Serine and Threonine Phosphorylation of the Paxillin LIM Domains Regulates Paxillin Focal Adhesion Localization and Cell Adhesion to Fibronectin

1998 ◽  
Vol 9 (7) ◽  
pp. 1803-1816 ◽  
Author(s):  
Michael C. Brown ◽  
Joseph A. Perrotta ◽  
Christopher E. Turner
Keyword(s):  
Cell Adhesion ◽  
Focal Adhesion ◽  
Binding Sites ◽  
Protein Localization ◽  
Model System ◽  
Lim Domain ◽  
Amino Terminal ◽  
Lim Domains ◽  
Inside Out

We have previously shown that the LIM domains of paxillin operate as the focal adhesion (FA)-targeting motif of this protein. In the current study, we have identified the capacity of paxillin LIM2 and LIM3 to serve as binding sites for, and substrates of serine/threonine kinases. The activities of the LIM2- and LIM3-associated kinases were stimulated after adhesion of CHO.K1 cells to fibronectin; consequently, a role for LIM domain phosphorylation in regulating the subcellular localization of paxillin after adhesion to fibronectin was investigated. An avian paxillin-CHO.K1 model system was used to explore the role of paxillin phosphorylation in paxillin localization to FAs. We found that mutations of paxillin that mimicked LIM domain phosphorylation accelerated fibronectin-induced localization of paxillin to focal contacts. Further, blocking phosphorylation of the LIM domains reduced cell adhesion to fibronectin, whereas constitutive LIM domain phosphorylation significantly increased the capacity of cells to adhere to fibronectin. The potentiation of FA targeting and cell adhesion to fibronectin was specific to LIM domain phosphorylation as mutation of the amino-terminal tyrosine and serine residues of paxillin that are phosphorylated in response to fibronectin adhesion had no effect on the rate of FA localization or cell adhesion. This represents the first demonstration of the regulation of protein localization through LIM domain phosphorylation and suggests a novel mechanism of regulating LIM domain function. Additionally, these results provide the first evidence that paxillin contributes to “inside-out” integrin-mediated signal transduction.

scholarly journals Distinct contributions of tensile and shear stress on E-cadherin levels during morphogenesis

2018 ◽  
Author(s):  
Girish R. Kale ◽  
Xingbo Yang ◽  
Jean-Marc Philippe ◽  
Madhav Mani ◽  
Pierre-François Lenne ◽  
...  
Keyword(s):  
Myosin Ii ◽  
Epithelial Morphogenesis ◽  
Shear Stresses ◽  
Mechanical Forces ◽  
Mechanical Tension ◽  
Tensile Forces ◽  
Axis Elongation ◽  
Persistent Cell ◽  
Adhesive Forces ◽  
E Cadherin

AbstractDuring epithelial morphogenesis, cell contacts (junctions) are constantly remodeled by mechanical forces that work against adhesive forces. E-cadherin complexes play a pivotal role in this process by providing persistent cell adhesion and by transmitting mechanical tension. In this context, it is unclear how mechanical forces affect E-cadherin adhesion and junction dynamics.During Drosophila embryo axis elongation, Myosin-II activity in the apico-medial and junctional cortex generates mechanical forces to drive junction remodeling. Here we report that the ratio between Vinculin and E-cadherin intensities acts as a ratiometric readout for these mechanical forces (load) at E-cadherin complexes. Medial Myosin-II loads E-cadherin complexes on all junctions, exerts tensile forces, and increases levels of E-cadherin. Junctional Myosin-II, on the other hand, biases the distribution of load between junctions of the same cell, exerts shear forces, and decreases the levels of E-cadherin. This work suggests distinct effects of tensile versus shear stresses on E-cadherin adhesion.

scholarly journals A Putative Catenin–Cadherin System Mediates Morphogenesis of the Caenorhabditis elegans Embryo

1998 ◽  
Vol 141 (1) ◽  
pp. 297-308 ◽  
Author(s):  
Michael Costa ◽  
William Raich ◽  
Cristina Agbunag ◽  
Ben Leung ◽  
Jeff Hardin ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Caenorhabditis Elegans ◽  
Cell Shape ◽  
Shape Change ◽  
Adherens Junctions ◽  
The Body ◽  
C Elegans ◽  
Cell Shape Change ◽  
Filament Bundles ◽  
Cell Adhesion Proteins

During morphogenesis of the Caenorhabditis elegans embryo, hypodermal (or epidermal) cells migrate to enclose the embryo in an epithelium and, subsequently, change shape coordinately to elongate the body (Priess, J.R., and D.I. Hirsh. 1986. Dev. Biol. 117:156– 173; Williams-Masson, E.M., A.N. Malik, and J. Hardin. 1997. Development [Camb.]. 124:2889–2901). We have isolated mutants defective in morphogenesis that identify three genes required for both cell migration during body enclosure and cell shape change during body elongation. Analyses of hmp-1, hmp-2, and hmr-1 mutants suggest that products of these genes anchor contractile actin filament bundles at the adherens junctions between hypodermal cells and, thereby, transmit the force of bundle contraction into cell shape change. The protein products of all three genes localize to hypodermal adherens junctions in embryos. The sequences of the predicted HMP-1, HMP-2, and HMR-1 proteins are related to the cell adhesion proteins α-catenin, β-catenin/Armadillo, and classical cadherin, respectively. This putative catenin–cadherin system is not essential for general cell adhesion in the C. elegans embryo, but rather mediates specific aspects of morphogenetic cell shape change and cytoskeletal organization.

E-cadherin N-glycosylation Modulates the Strength of Adherens Junctions

2010 ◽  
Author(s):  
Sarah J. Shareef ◽  
Mihai Nita-Lazar ◽  
Maria A. Kukuruzinska
Keyword(s):  
Cell Adhesion ◽  
Cancer Cells ◽  
Solid Tumor ◽  
Adherens Junctions ◽  
The Body ◽  
Junction Formation ◽  
E Cadherin

Metastasis, the spread of cancer cells throughout the body, claims 90% of solid tumor deaths. During metastasis, cancer cells undergo discohesion. An understanding of how to control and strengthen cell adhesion through junction formation could lead to methods for decreasing metastatic tendencies.

Epithelial Morphogenesis Driven by Cell-Matrix vs. Cell-Cell Adhesion

2020 ◽  
Author(s):  
Shaohe Wang ◽  
Kazue Matsumoto ◽  
Kenneth M. Yamada
Keyword(s):  
Cell Adhesion ◽  
Epithelial Morphogenesis ◽  
Cell Matrix ◽  
Cell Cell

scholarly journals Two LIM Domain Proteins and UNC-96 Link UNC-97/PINCH to Myosin Thick Filaments in Caenorhabditis elegans Muscle

2007 ◽  
Vol 18 (11) ◽  
pp. 4317-4326 ◽  
Author(s):  
Hiroshi Qadota ◽  
Kristina B. Mercer ◽  
Rachel K. Miller ◽  
Kozo Kaibuchi ◽  
Guy M. Benian
Keyword(s):  
Caenorhabditis Elegans ◽  
Binding Assays ◽  
Lim Domain ◽  
Yeast Two Hybrid ◽  
Lim Domains ◽  
Thick Filaments ◽  
Vitro Binding ◽  
Two Hybrid ◽  
Hybrid Screening

By yeast two-hybrid screening, we found three novel interactors (UNC-95, LIM-8, and LIM-9) for UNC-97/PINCH in Caenorhabditis elegans. All three proteins contain LIM domains that are required for binding. Among the three interactors, LIM-8 and LIM-9 also bind to UNC-96, a component of sarcomeric M-lines. UNC-96 and LIM-8 also bind to the C-terminal portion of a myosin heavy chain (MHC), MHC A, which resides in the middle of thick filaments in the proximity of M-lines. All interactions identified by yeast two-hybrid assays were confirmed by in vitro binding assays using purified proteins. All three novel UNC-97 interactors are expressed in body wall muscle and by antibodies localize to M-lines. Either a decreased or an increased dosage of UNC-96 results in disorganization of thick filaments. Our previous studies showed that UNC-98, a C2H2 Zn finger protein, acts as a linkage between UNC-97, an integrin-associated protein, and MHC A in myosin thick filaments. In this study, we demonstrate another mechanism by which this linkage occurs: from UNC-97 through LIM-8 or LIM-9/UNC-96 to myosin.

scholarly journals Keloidal pathophysiology: Current notions

2021 ◽  
Vol 7 ◽  
pp. 205951312098032
Author(s):  
Chenyu Huang ◽  
Rei Ogawa
Keyword(s):  
Web Of Science ◽  
English Literature ◽  
The Body ◽  
Mechanical Forces ◽  
Healthy Skin ◽  
Level Of Evidence ◽  
Extracellular Matrix Components ◽  
Keloid Formation ◽  
Mechanical Factors ◽  
Pathological Scar

Introduction: Keloids are pathological scars that are notorious for their chronic and relentless invasion into adjacent healthy skin, with commonly seen post-therapeutic recurrence after monotherapies. Methods: An English literature review on keloid pathophysiology was performed by searching the PubMed, Embase and Web of Science databases, to find out the up-to-date relevant articles. The level of evidence was evaluated based on the included studies with the highest level of evidence first. Results: Keloid morphology, signs, symptoms and the histopathological changes that occur in the local cells and extracellular matrix components are described. The theories on the pathophysiology of keloidogenesis that have been proposed to date are also covered; these include endocrinological, nutritional, vascular, and autoimmunological factors. In addition, we describe the local mechanical forces (and the mechanosignalling pathways by which these forces shape keloid cell activities) that promote keloid formation and determine the direction of invasion of keloids and the body sites that are prone to them. Conclusion: A better understanding of this pathological entity, particularly its mechanobiology, will aid the development of new diagnostic and therapeutic strategies for use in the clinic to prevent, reduce or even reverse the growth of this pathological scar. Lay Summary Keloids are skin scars that are famous for their chronic invasion into healthy skin, with commonly seen recurrence after surgeries. Cells such as lymphocytes, macrophages, mast cells and endothelial cells are involved in keloid growth. Particularly, endocrinological, nutritional, vascular, autoimmunological and mechanical factors actively take part in keloid progression.

scholarly journals Epithelial Protein Lost in Neoplasm, EPLIN, the Cellular and Molecular Prospects in Cancers

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1038
Author(s):  
Jianyuan Zeng ◽  
Wen G. Jiang ◽  
Andrew J. Sanders
Keyword(s):  
The Body ◽  
Early Years ◽  
Actin Binding ◽  
Cell Cycle Gene ◽  
Lim Domain ◽  
The Past ◽  
Concise Review ◽  
Cancerous Cell ◽  
Cytoskeletal Dynamics ◽  
In Cells

Epithelial Protein Lost In Neoplasm (EPLIN), also known as LIMA1 (LIM Domain And Actin Binding 1), was first discovered as a protein differentially expressed in normal and cancerous cell lines. It is now known to be key to the progression and metastasis of certain solid tumours. Despite a slow pace in understanding the biological role in cells and body systems, as well as its clinical implications in the early years since its discovery, recent years have witnessed a rapid progress in understanding the mechanisms of this protein in cells, diseases and indeed the body. EPLIN has drawn more attention over the past few years with its roles expanding from cell migration and cytoskeletal dynamics, to cell cycle, gene regulation, angiogenesis/lymphangiogenesis and lipid metabolism. This concise review summarises and discusses the recent progress in understanding EPLIN in biological processes and its implications in cancer.

scholarly journals Myosin VI plays a role in cell–cell adhesion during epithelial morphogenesis

2004 ◽  
Vol 121 (11) ◽  
pp. 1335-1351 ◽  
Author(s):  
Hadas Millo ◽  
Kevin Leaper ◽  
Vasiliki Lazou ◽  
Mary Bownes
Keyword(s):  
Cell Adhesion ◽  
Epithelial Morphogenesis ◽  
Myosin Vi ◽  
Cell Cell

scholarly journals PDZ and LIM Domain-Encoding Genes: Molecular Interactions and their Role in Development

2007 ◽  
Vol 7 ◽  
pp. 1470-1492 ◽  
Author(s):  
Aartjan J. W. te Velthuis ◽  
Christoph P. Bagowski
Keyword(s):  
Current Knowledge ◽  
Pdz Domain ◽  
Cell Lineage ◽  
Lim Domain ◽  
Specific Expression ◽  
Cytoskeleton Organization ◽  
Signaling Complex ◽  
Lim Domains ◽  
Gene Structures ◽  
Encoding Genes

PDZ/LIM genes encode a group of proteins that play very important, but diverse, biological roles. They have been implicated in numerous vital processes, e.g., cytoskeleton organization, neuronal signaling, cell lineage specification, organ development, and oncogenesis.In mammals, there are ten genes that encode for both a PDZ domain, and one or several LIM domains: four genes of the ALP subfamily (ALP, Elfin, Mystique, and RIL), three of the Enigma subfamily (Enigma, Enigma Homolog, and ZASP), the two LIM kinases (LIMK1 and LIMK2), and the LIM only protein 7 (LMO7). Functionally, all PDZ and LIM domain proteins share an important trait, i.e., they can associate with and/or influence the actin cytoskeleton.We review here the PDZ and LIM domain—encoding genes and their different gene structures, their binding partners, and their role in development and disease. Emphasis is laid on the important questions: why the combination of a PDZ domain with one or more LIM domains is found in such a diverse group of proteins, and what role the PDZ/LIM module could have in signaling complex assembly and localization.Furthermore, the current knowledge on splice form specific expression and the function of these alternative transcripts during vertebrate development will be discussed, since another source of complexity for the PDZ and LIM domain—encoding proteins is introduced by alternative splicing, which often creates different domain combinations.

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