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Journal of Cellular Physiology Jun 2023The microtubule cytoskeleton plays a critical role in a variety of cellular activities, and its structures and functions have been extensively studied. However, little... (Review)
Review
The microtubule cytoskeleton plays a critical role in a variety of cellular activities, and its structures and functions have been extensively studied. However, little is known about cell differentiation-related microtubule remodeling, its regulatory mechanisms, and its physiological functions. Recent studies have shown that microtubule-binding proteins as well as cell junctions, such as desmosomes and adherens junctions, are involved in the remodeling of microtubules in response to cell differentiation. In addition, the microtubule-organizing activity and structural integrity of centrosomes undergo dramatic changes during cell differentiation to promote microtubule remodeling. Here we summarize recent advances revealing the dynamic changes in microtubule organization and functions during cell differentiation. We also highlight the molecular mechanisms underlying microtubule modeling in differentiated cells, focusing on the key roles played by microtubule-binding proteins, cell junctions, and centrosomes.
Topics: Adherens Junctions; Cell Differentiation; Centrosome; Cytoskeleton; Microtubules
PubMed: 36960617
DOI: 10.1002/jcp.31011 -
Developmental Dynamics : An Official... Mar 2016In epithelial tissues, cells constantly generate and transmit forces between each other. Forces generated by the actomyosin cytoskeleton regulate tissue shape and... (Review)
Review
In epithelial tissues, cells constantly generate and transmit forces between each other. Forces generated by the actomyosin cytoskeleton regulate tissue shape and structure and also provide signals that influence cells' decisions to divide, die, or differentiate. Forces are transmitted across epithelia because cells are mechanically linked through junctional complexes, and forces can propagate through the cell cytoplasm. Here, we review some of the molecular mechanisms responsible for force generation, with a specific focus on the actomyosin cortex and adherens junctions. We then discuss evidence for how these mechanisms promote cell shape changes and force transmission in tissues.
Topics: Actomyosin; Adherens Junctions; Animals; Cell Division; Epithelial Cells; Epithelium; Humans
PubMed: 26756938
DOI: 10.1002/dvdy.24384 -
Trends in Biochemical Sciences Feb 2016The actin cytoskeleton and adhesion junctions are physically and functionally coupled at the cell-cell interface between epithelial cells. The actin regulatory complex... (Review)
Review
The actin cytoskeleton and adhesion junctions are physically and functionally coupled at the cell-cell interface between epithelial cells. The actin regulatory complex Arp2/3 has an established role in the turnover of junctional actin; however, the role of formins, the largest group of actin regulators, is less clear. Formins dynamically shape the actin cytoskeleton and have various functions within cells. In this review we describe recent progress on how formins regulate actin dynamics at cell-cell contacts and highlight formin functions during polarized protein traffic necessary for epithelialization.
Topics: Actin Cytoskeleton; Adherens Junctions; Animals; Epithelium; Humans
PubMed: 26732401
DOI: 10.1016/j.tibs.2015.12.002 -
Developmental Cell Oct 2018During epithelial tissue development, repair, and homeostasis, adherens junctions (AJs) ensure intercellular adhesion and tissue integrity while allowing for cell and... (Review)
Review
During epithelial tissue development, repair, and homeostasis, adherens junctions (AJs) ensure intercellular adhesion and tissue integrity while allowing for cell and tissue dynamics. Mechanical forces play critical roles in AJs' composition and dynamics. Recent findings highlight that beyond a well-established role in reinforcing cell-cell adhesion, AJ mechanosensitivity promotes junctional remodeling and polarization, thereby regulating critical processes such as cell intercalation, division, and collective migration. Here, we provide an integrated view of mechanosensing mechanisms that regulate cell-cell contact composition, geometry, and integrity under tension and highlight pivotal roles for mechanosensitive AJ remodeling in preserving epithelial integrity and sustaining tissue dynamics.
Topics: Adherens Junctions; Animals; Cadherins; Cell Adhesion; Epithelial Cells; Epithelium; Humans; Mechanotransduction, Cellular; Morphogenesis
PubMed: 30300588
DOI: 10.1016/j.devcel.2018.09.014 -
Experimental Cell Research Sep 2017Cell-cell adhesions are critical for the development and maintenance of tissues. Present at sites of cell-cell contact are the adherens junctions and tight junctions.... (Review)
Review
Cell-cell adhesions are critical for the development and maintenance of tissues. Present at sites of cell-cell contact are the adherens junctions and tight junctions. The adherens junctions mediate cell-cell adhesion via the actions of nectins and cadherins. The tight junctions regulate passage of ions and small molecules between cells and establish cell polarity. Historically, the adherens and tight junctions have been thought of as discrete complexes. However, it is now clear that a high level of interdependency exists between the two junctional complexes. The adherens junctions and tight junctions are physically linked, by the zonula occludens proteins, and linked via signaling molecules including several polarity complexes and actin cytoskeletal modifiers. This review will first describe the individual components of both the adherens and tight junctions and then discuss the coupling of the two complexes with an emphasis on the signaling links and physical interactions between the two junctional complexes.
Topics: Adherens Junctions; Animals; Cadherins; Cell Membrane; Cell Polarity; Cytoskeleton; Humans; Tight Junctions
PubMed: 28372972
DOI: 10.1016/j.yexcr.2017.03.061 -
Tissue Barriers Oct 2023Tight junctions (TJs) are the most apical components of junctional complexes in epithelial and endothelial cells. Barrier function is one of the major functions of TJ,... (Review)
Review
Tight junctions (TJs) are the most apical components of junctional complexes in epithelial and endothelial cells. Barrier function is one of the major functions of TJ, which restricts the ions and small water-soluble molecules from passing through the paracellular pathway. Adherens junctions (AJs) play an important role in cell-cell adhesion and cell signaling. Gap junctions (GJs) are intercellular channels regulating electrical and metabolic signals between cells. It is well known that TJ integral membrane proteins, such as claudins and occludins, are the molecular building blocks responsible for TJ barrier function. However, recent studies demonstrate that proteins of other junctional complexes can influence and regulate TJ barrier function. Therefore, the crosstalk between different cell junctions represents a common means to modulate cellular activities. In this review, we will discuss the interactions among TJ, AJ, and GJ by focusing on how AJ and GJ proteins regulate TJ barrier function in different biological systems.
Topics: Tight Junctions; Epithelial Cells; Endothelial Cells; Intercellular Junctions; Adherens Junctions
PubMed: 36220768
DOI: 10.1080/21688370.2022.2133880 -
Experimental Cell Research Sep 2017Endothelial cells line blood vessels and provide a dynamic interface between the blood and tissues. They remodel to allow leukocytes, fluid and small molecules to enter... (Review)
Review
Endothelial cells line blood vessels and provide a dynamic interface between the blood and tissues. They remodel to allow leukocytes, fluid and small molecules to enter tissues during inflammation and infections. Here we compare the signaling networks that contribute to endothelial permeability and leukocyte transendothelial migration, focusing particularly on signals mediated by small GTPases that regulate cell adhesion and the actin cytoskeleton. Rho and Rap GTPase signaling is important for both processes, but they differ in that signals are activated locally under leukocytes, whereas endothelial permeability is a wider event that affects the whole cell. Some molecules play a unique role in one of the two processes, and could therefore be targeted to selectively alter either endothelial permeability or leukocyte transendothelial migration.
Topics: Actins; Adherens Junctions; Animals; Cell Adhesion; Endothelial Cells; Humans; Leukocytes; Signal Transduction
PubMed: 28602626
DOI: 10.1016/j.yexcr.2017.06.003 -
The Journal of Cell Biology Jul 2023The mechanisms that regulate the spatial sorting of nonmuscle myosins-2 (NM2) isoforms and couple them mechanically to the plasma membrane are unclear. Here we show that...
The mechanisms that regulate the spatial sorting of nonmuscle myosins-2 (NM2) isoforms and couple them mechanically to the plasma membrane are unclear. Here we show that the cytoplasmic junctional proteins cingulin (CGN) and paracingulin (CGNL1) interact directly with NM2s through their C-terminal coiled-coil sequences. CGN binds strongly to NM2B, and CGNL1 to NM2A and NM2B. Knockout (KO), exogenous expression, and rescue experiments with WT and mutant proteins show that the NM2-binding region of CGN is required for the junctional accumulation of NM2B, ZO-1, ZO-3, and phalloidin-labeled actin filaments, and for the maintenance of tight junction membrane tortuosity and apical membrane stiffness. CGNL1 expression promotes the junctional accumulation of both NM2A and NM2B and its KO results in myosin-dependent fragmentation of adherens junction complexes. These results reveal a mechanism for the junctional localization of NM2A and NM2B and indicate that, by binding to NM2s, CGN and CGNL1 mechanically couple the actomyosin cytoskeleton to junctional protein complexes to mechanoregulate the plasma membrane.
Topics: Adherens Junctions; Cell Membrane; Cytoskeletal Proteins; Cytoskeleton; Myosins; Tight Junctions
PubMed: 37204781
DOI: 10.1083/jcb.202208065 -
Cold Spring Harbor Perspectives in... May 2018The Hippo signal transduction pathway is an important regulator of organ growth and cell differentiation, and its deregulation contributes to the development of cancer.... (Review)
Review
The Hippo signal transduction pathway is an important regulator of organ growth and cell differentiation, and its deregulation contributes to the development of cancer. The activity of the Hippo pathway is strongly dependent on cell junctions, cellular architecture, and the mechanical properties of the microenvironment. In this review, we discuss recent advances in our understanding of how cell junctions transduce signals from the microenvironment and control the activity of the Hippo pathway. We also discuss how these mechanisms may control organ growth during development and regeneration, and how defects in them deregulate Hippo signaling in cancer cells.
Topics: Adherens Junctions; Animals; Cell Differentiation; Cell Proliferation; Cellular Microenvironment; Cytoskeleton; Hippo Signaling Pathway; Intercellular Junctions; Models, Biological; Protein Serine-Threonine Kinases; Signal Transduction; Tight Junctions
PubMed: 28600393
DOI: 10.1101/cshperspect.a028753 -
Cell Biology International Mar 2016Cell-matrix adhesion and cell-cell contacts are essential for the metabolism, protein synthesis, survival, and cancer metastasis of cells. Major transmembrane receptors... (Review)
Review
Cell-matrix adhesion and cell-cell contacts are essential for the metabolism, protein synthesis, survival, and cancer metastasis of cells. Major transmembrane receptors are the integrins, which are responsible for cell-matrix adhesions, and the cadherins, which are important for cell-cell adhesions. Adherent cells anchor via focal adhesion proteins to the extracellular matrix, whereas cell-cell contacts connect via focal adherens junction proteins. The temporal formation of these connections is greatly strengthened either through externally applied stresses on the cell or by myosin-driven cell contractility. The mechanism by which protein(s) within these connections sense, transmit, and respond to mechanochemical signaling is currently strongly debated and various candidates have been named. Vinculin has been described as one of the key players in cell-matrix and cell-cell adhesions that build a strong physical connection for transmitting forces between the cytoskeleton, the extracellular matrix, and cell-cell connections.
Topics: Actins; Adherens Junctions; Cell Adhesion; Crk-Associated Substrate Protein; Extracellular Matrix; Humans; Integrins; Mechanotransduction, Cellular; Protein Binding; Vinculin
PubMed: 26909547
DOI: 10.1002/cbin.10563