Tuning of Protein Kinase Circuitry by p38α Is Vital for Epithelial Tissue Homeostasis

Plasticity of the resilient keratin intermediate filament cytoskeleton is an important prerequisite for epithelial tissue homeostasis. Here, the contribution of stress-activated p38 MAPK to keratin network organization was examined in cultured cells. It was observed that phosphorylated p38 colocalized with keratin granules that were rapidly formed in response to orthovanadate. The same p38p recruitment was noted during mitosis, in various stress situations and in cells producing mutant keratins. In all these situations keratin 8 became phosphorylated on S73, a well-known p38 target site. To demonstrate that p38-dependent keratin phosphorylation determines keratin organization, p38 activity was pharmacologically and genetically modulated: up-regulation induced keratin granule formation, whereas down-regulation prevented keratin filament network disassembly. Furthermore, transient p38 inhibition also inhibited keratin filament precursor formation and mutant keratin granule dissolution. Collectively, the rapid and reversible effects of p38 activity on keratin phosphorylation and organization in diverse physiological, stress, and pathological situations identify p38-dependent signalling as a major intermediate filament–regulating pathway.

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Tu1774 - A Critical Role for the Sympathetic Nervous System in Maintaining Intestinal Epithelial Tissue Homeostasis and Mucosal Barrier Function

Gastroenterology ◽

10.1016/s0016-5085(18)33400-0 ◽

2018 ◽

Vol 154 (6) ◽

pp. S-1016

Author(s):

Anne S. ten Hove ◽

Rose Willemze ◽

Patricia van Hamersveld ◽

Olaf Welting ◽

Wouter J. de Jonge

Keyword(s):

Nervous System ◽

Sympathetic Nervous System ◽

Barrier Function ◽

Critical Role ◽

Tissue Homeostasis ◽

Mucosal Barrier ◽

Epithelial Tissue ◽

Intestinal Epithelial ◽

Mucosal Barrier Function ◽

Sympathetic Nervous

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Chlamydia trachomatis Disturbs Epithelial Tissue Homeostasis in Fallopian Tubes via Paracrine Wnt Signaling

American Journal Of Pathology ◽

10.1016/j.ajpath.2011.09.015 ◽

2012 ◽

Vol 180 (1) ◽

pp. 186-198 ◽

Cited By ~ 42

Author(s):

Mirjana Kessler ◽

Julia Zielecki ◽

Oliver Thieck ◽

Hans-Joachim Mollenkopf ◽

Christina Fotopoulou ◽

...

Keyword(s):

Chlamydia Trachomatis ◽

Wnt Signaling ◽

Tissue Homeostasis ◽

Epithelial Tissue ◽

Fallopian Tubes

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Flexibility sustains epithelial tissue homeostasis

Current Opinion in Cell Biology ◽

10.1016/j.ceb.2019.04.009 ◽

2019 ◽

Vol 60 ◽

pp. 84-91 ◽

Cited By ~ 7

Author(s):

Karen Tai ◽

Katie Cockburn ◽

Valentina Greco

Keyword(s):

Tissue Homeostasis ◽

Epithelial Tissue

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Mechanics of Epithelial Tissue Homeostasis and Morphogenesis

Science ◽

10.1126/science.1235249 ◽

2013 ◽

Vol 340 (6137) ◽

pp. 1185-1189 ◽

Cited By ~ 331

Author(s):

Charlène Guillot ◽

Thomas Lecuit

Keyword(s):

Epithelial Cells ◽

Tissue Homeostasis ◽

Pivotal Role ◽

Epithelial Tissue ◽

Fluid Behavior ◽

Functional Tissue ◽

Vital Functions ◽

Mechanical Basis ◽

Tight Association

Epithelia are robust tissues that support the structure of embryos and organs and serve as effective barriers against pathogens. Epithelia also chemically separate different physiological environments. These vital functions require tight association between cells through the assembly of junctions that mechanically stabilize the tissue. Remarkably, epithelia are also dynamic and can display a fluid behavior. Cells continuously die or divide, thereby allowing functional tissue homeostasis. Epithelial cells can change shape or intercalate as tissues deform during morphogenesis. We review the mechanical basis of tissue robustness and fluidity, with an emphasis on the pivotal role of junction dynamics. Tissue fluidity emerges from local active stresses acting at cell interfaces and allows the maintenance of epithelial organization during morphogenesis and tissue renewal.

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RNF43/ZNRF3 negatively regulates taste tissue homeostasis and positively regulates dorsal lingual epithelial tissue homeostasis

Stem Cell Reports ◽

10.1016/j.stemcr.2021.12.002 ◽

2022 ◽

Author(s):

Chanyi Lu ◽

Xiaoli Lin ◽

Jumpei Yamashita ◽

Ranhui Xi ◽

Minliang Zhou ◽

...

Keyword(s):

Tissue Homeostasis ◽

Epithelial Tissue

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Mechanical Regulation of Epithelial Tissue Homeostasis

Physical Review X ◽

10.1103/physrevx.11.031029 ◽

2021 ◽

Vol 11 (3) ◽

Author(s):

Sara Kaliman ◽

Maxime Hubert ◽

Carina Wollnik ◽

Lovro Nuić ◽

Damir Vurnek ◽

...

Keyword(s):

Tissue Homeostasis ◽

Epithelial Tissue ◽

Mechanical Regulation

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A role for the actin cytoskeleton in the hormonal and growth-factor-mediated activation of protein kinase B

Biochemical Journal ◽

10.1042/0264-6021:3530735v ◽

2001 ◽

Vol 353 (3) ◽

pp. 735

Author(s):

K. PEYROLLIER ◽

E. HAJDUCH ◽

A. GRAY ◽

G. J. LITHERLAND ◽

A. R. PRESCOTT ◽

...

Keyword(s):

Growth Factor ◽

Protein Kinase ◽

Actin Cytoskeleton ◽

Protein Kinase B

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Early signalling events of autophagy

Essays in Biochemistry ◽

10.1042/bse0550001 ◽

2013 ◽

Vol 55 ◽

pp. 1-15 ◽

Cited By ~ 16

Author(s):

Laura E. Gallagher ◽

Edmond Y.W. Chan

Keyword(s):

Protein Kinase ◽

Focal Adhesion Kinase ◽

Focal Adhesion ◽

Mammalian Cells ◽

Mammalian Target Of Rapamycin ◽

Interacting Protein ◽

The Core ◽

Autophagy Gene ◽

Autophagy Induction ◽

Cellular Pathways

Autophagy is a conserved cellular degradative process important for cellular homoeostasis and survival. An early committal step during the initiation of autophagy requires the actions of a protein kinase called ATG1 (autophagy gene 1). In mammalian cells, ATG1 is represented by ULK1 (uncoordinated-51-like kinase 1), which relies on its essential regulatory cofactors mATG13, FIP200 (focal adhesion kinase family-interacting protein 200 kDa) and ATG101. Much evidence indicates that mTORC1 [mechanistic (also known as mammalian) target of rapamycin complex 1] signals downstream to the ULK1 complex to negatively regulate autophagy. In this chapter, we discuss our understanding on how the mTORC1–ULK1 signalling axis drives the initial steps of autophagy induction. We conclude with a summary of our growing appreciation of the additional cellular pathways that interconnect with the core mTORC1–ULK1 signalling module.

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Spatial control of actin-based motility through plasmalemmal PtdIns(4,5)P2-rich raft assemblies.

Biochemical Society Symposium ◽

10.1042/bss0720119 ◽

2005 ◽

Vol 72 ◽

pp. 119-127 ◽

Cited By ~ 19

Author(s):

Tamara Golub ◽

Caroni Pico

Keyword(s):

Protein Kinase ◽

Cell Surface ◽

Actin Cytoskeleton ◽

Lipid Rafts ◽

Patch Clustering ◽

Pkc Protein Kinase C ◽

Membrane Bound ◽

And Function ◽

Cytoskeleton Dynamics ◽

Syndrome Protein

The interactions of cells with their environment involve regulated actin-based motility at defined positions along the cell surface. Sphingolipid- and cholesterol-dependent microdomains (rafts) order proteins at biological membranes, and have been implicated in most signalling processes at the cell surface. Many membrane-bound components that regulate actin cytoskeleton dynamics and cell-surface motility associate with PtdIns(4,5)P2-rich lipid rafts. Although raft integrity is not required for substrate-directed cell spreading, or to initiate signalling for motility, it is a prerequisite for sustained and organized motility. Plasmalemmal rafts redistribute rapidly in response to signals, triggering motility. This process involves the removal of rafts from sites that are not interacting with the substrate, apparently through endocytosis, and a local accumulation at sites of integrin-mediated substrate interactions. PtdIns(4,5)P2-rich lipid rafts can assemble into patches in a process depending on PtdIns(4,5)P2, Cdc42 (cell-division control 42), N-WASP (neural Wiskott-Aldrich syndrome protein) and actin cytoskeleton dynamics. The raft patches are sites of signal-induced actin assembly, and their accumulation locally promotes sustained motility. The patches capture microtubules, which promote patch clustering through PKA (protein kinase A), to steer motility. Raft accumulation at the cell surface, and its coupling to motility are influenced greatly by the expression of intrinsic raft-associated components that associate with the cytosolic leaflet of lipid rafts. Among them, GAP43 (growth-associated protein 43)-like proteins interact with PtdIns(4,5)P2 in a Ca2+/calmodulin and PKC (protein kinase C)-regulated manner, and function as intrinsic determinants of motility and anatomical plasticity. Plasmalemmal PtdIns(4,5)P2-rich raft assemblies thus provide powerful organizational principles for tight spatial and temporal control of signalling in motility.

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