The role of apical cell–cell junctions and associated cytoskeleton in mechanotransduction

Abstract

Tissues of multicellular organisms are characterised by several types of specialised cell-cell junctions. In vertebrate epithelia and endothelia, tight and adherens junctions (AJ) play critical roles in barrier and adhesion functions, and are connected to the actin and microtubule cytoskeletons. The interaction between junctions and the cytoskeleton is crucial for tissue development and physiology, and is involved in the molecular mechanisms governing cell shape, motility, growth and signalling. The machineries which functionally connect tight and AJ to the cytoskeleton comprise proteins which either bind directly to cytoskeletal filaments, or function as adaptors for regulators of the assembly and function of the cytoskeleton. In the last two decades, specific cytoskeleton-associated junctional molecules have been implicated in mechanotransduction, revealing the existence of multimolecular complexes that can sense mechanical cues and translate them into adaptation to tensile forces and biochemical signals. Here, we summarise the current knowledge about the machineries that link tight and AJ to actin filaments and microtubules, and the molecular basis for mechanotransduction at epithelial and endothelial AJ.

Decreased E‐Cadherin in MCF7 Human Breast Cancer Cells Forming Multicellular Spheroids Exposed to Simulated Microgravity

“…As shown in Figure , the way that cells contact their neighbors or the bottom of the culture flask is different in MCS and AD cells, although the gravitational forces acting on the cells are similar. Attachment of cells to their solid environment is either mediated by ECM proteins or occurs by direct cell–cell interaction via various types of so‐called junctions . Only three of the more than 300 ECM proteins were detected in MCS formed on the RPM with at least twofold enhanced LFQ values (Table ).…”

“…Attachment of cells to their solid environment is either mediated by ECM proteins or occurs by direct cell-cell interaction via various types of so-called junctions. [49] Only three of the more than 300 ECM proteins were detected in MCS formed on the RPM with at least twofold enhanced LFQ values ( Table 2). Therefore, we evaluated the junction proteins in more detail.…”

Claudin Loss-of-Function Disrupts Tight Junctions and Impairs Amelogenesis

“…This interaction allows direct or indirect bonding to actin, anchoring the TJ within the underlying cytoskeleton. This scaffold facilitates the assembly of highly ordered structures, such as junctional complexes, regulating epithelial cell polarity, proliferation and differentiation (Sluysmans et al, 2017). This is consistent with our data showing a disturbed actin filament network at apical end of ameloblasts and a more diffused ZO-1 labeling in Claudin-16 KO mice (Bardet et al, 2016).…”

In situ molecular characterization of endoneurial microvessels that form the blood‐nerve barrier in normal human adult peripheral nerves

“…Claudin‐5 (CLDN5), zona occludens‐1 (ZO‐1, also known as tight junction protein‐1 [TJP1]), and the vascular‐specific cadherin‐5 (CDH5, also known as vascular endothelial [VE]‐cadherin), are commonly cited as molecular components of the specialized BNB junctional complex, with alterations implicated in the pathogenesis of specific peripheral neuropathies . However, data have emerged over the past decade on the complexity of specialized intercellular tight and adherens junctional complexes formed by specific claudins and cadherins interacting with adapter molecules such members of the ZO‐1 subfamily, catenins, and other membrane‐associated junctional proteins that bind directly or indirectly to cytoskeletal proteins and are responsible for the cellular structural integrity, polarity, and the unique biologic functions during normal physiological states …”

“…[6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] However, data have emerged over the past decade on the complexity of specialized intercellular tight and adherens junctional complexes formed by specific claudins and cadherins interacting with adapter molecules such members of the ZO-1 subfamily, catenins, and other membrane-associated junctional proteins that bind directly or indirectly to cytoskeletal proteins and are responsible for the cellular structural integrity, polarity, and the unique biologic functions during normal physiological states. 7,[23][24][25][26][27] Our recent work that established the normal adult human BNB transcriptome based on transcripts universally expressed by whole exome sequencing of laser capture microdissected endoneurial microvessels coupled to early-and late-passage primary human endoneurial endothelial cells, with some in situ validation of protein expression on endoneurial endothelium by indirect immunohistochemistry, ascertained 133 transcripts that may be involved in the intercellular junctional complex, as well as 509 transporter transcripts that may be responsible for the influx or efflux of solutes, macromolecules, and xenobiotics by the normal adult human BNB. 24 In order to better understand how the human BNB develops, is maintained in health and the functional alterations and adaptations that may occur in disease states such as peripheral neuropathies and traumatic injury, it is essential to determine its specific molecular components prior to elucidating biologically relevant signaling mechanisms.…”