scholarly journals Cytoskeleton in motion: the dynamics of keratin intermediate filaments in epithelia

2011 ◽  
Vol 194 (5) ◽  
pp. 669-678 ◽  
Author(s):  
Reinhard Windoffer ◽  
Michael Beil ◽  
Thomas M. Magin ◽  
Rudolf E. Leube
Keyword(s):  
Intermediate Filaments ◽  
Molecular Mechanisms ◽  
Protein Biosynthesis ◽  
Epithelial Tissue ◽  
Multistep Process ◽  
Keratin Filament ◽  
Cell Type Specific ◽  
Cytoskeletal Networks ◽  
Microtubule Networks ◽  
Keratin Intermediate Filaments

Epithelia are exposed to multiple forms of stress. Keratin intermediate filaments are abundant in epithelia and form cytoskeletal networks that contribute to cell type–specific functions, such as adhesion, migration, and metabolism. A perpetual keratin filament turnover cycle supports these functions. This multistep process keeps the cytoskeleton in motion, facilitating rapid and protein biosynthesis–independent network remodeling while maintaining an intact network. The current challenge is to unravel the molecular mechanisms underlying the regulation of the keratin cycle in relation to actin and microtubule networks and in the context of epithelial tissue function.

scholarly journals 14-3-3 recruits keratin intermediate filaments to mechanically sensitive cell-cell contacts

2018 ◽  
Author(s):  
Richard A. Mariani ◽  
Shalaka Paranjpe ◽  
Radek Dobrowolski ◽  
Gregory F. Weber
Keyword(s):  
Intermediate Filaments ◽  
Intermediate Filament ◽  
Cell Junctions ◽  
Fusion Construct ◽  
Cell Contacts ◽  
Keratin 19 ◽  
Keratin Filament ◽  
Cytoskeletal Networks ◽  
Keratin Intermediate Filaments ◽  
Cell Cell

AbstractIntermediate filament cytoskeletal networks simultaneously support mechanical integrity and influence signal transduction pathways. Marked remodeling of the keratin intermediate filament network accompanies collective cellular morphogenetic movements that occur during early embryonic development in the frog Xenopus laevis. While this reorganization of keratin is initiated by force transduction on cell-cell contacts mediated by C-cadherin, the mechanism by which keratin filament reorganization occurs remains poorly understood. In this work we demonstrate that 14-3-3 proteins regulate keratin reorganization dynamics in embryonic mesendoderm cells from Xenopus gastrula. 14-3-3 co-localizes with keratin filaments near cell-cell junctions in migrating mesendoderm. Co-immunoprecipitation, mass spectrometry and bioinformatic analyses indicate Keratin 19 is a target of 14-3-3 in the whole embryo and, more specifically, mesendoderm tissue. Inhibition of 14-3-3 results in both the decreased exchange of keratin subunits into filaments and blocks keratin filament recruitment toward cell-cell contacts. Synthetically coupling 14-3-3 to Keratin 19 through a unique fusion construct conversely induces the localization of this keratin population to the region of cell-cell contacts. Taken together, these findings indicate that 14-3-3 acts on keratin intermediate filaments and is involved in their reorganization to sites of cell adhesion.

scholarly journals Shisa6 mediates cell-type specific regulation of depression in the nucleus accumbens

2021 ◽  
Author(s):  
Hee-Dae Kim ◽  
Jing Wei ◽  
Tanessa Call ◽  
Nicole Teru Quintus ◽  
Alexander J. Summers ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Current Treatment ◽  
Specific Cell ◽  
Excitatory Synapses ◽  
Cell Type ◽  
Cell Type Specific ◽  
Specific Regulation ◽  
Circuit Function

AbstractDepression is the leading cause of disability and produces enormous health and economic burdens. Current treatment approaches for depression are largely ineffective and leave more than 50% of patients symptomatic, mainly because of non-selective and broad action of antidepressants. Thus, there is an urgent need to design and develop novel therapeutics to treat depression. Given the heterogeneity and complexity of the brain, identification of molecular mechanisms within specific cell-types responsible for producing depression-like behaviors will advance development of therapies. In the reward circuitry, the nucleus accumbens (NAc) is a key brain region of depression pathophysiology, possibly based on differential activity of D1- or D2- medium spiny neurons (MSNs). Here we report a circuit- and cell-type specific molecular target for depression, Shisa6, recently defined as an AMPAR component, which is increased only in D1-MSNs in the NAc of susceptible mice. Using the Ribotag approach, we dissected the transcriptional profile of D1- and D2-MSNs by RNA sequencing following a mouse model of depression, chronic social defeat stress (CSDS). Bioinformatic analyses identified cell-type specific genes that may contribute to the pathogenesis of depression, including Shisa6. We found selective optogenetic activation of the ventral tegmental area (VTA) to NAc circuit increases Shisa6 expression in D1-MSNs. Shisa6 is specifically located in excitatory synapses of D1-MSNs and increases excitability of neurons, which promotes anxiety- and depression-like behaviors in mice. Cell-type and circuit-specific action of Shisa6, which directly modulates excitatory synapses that convey aversive information, identifies the protein as a potential rapid-antidepressant target for aberrant circuit function in depression.

scholarly journals Feeding a Saccharomyces cerevisiae fermentation product improves udder health and immune response to a Streptococcus uberis mastitis challenge in mid-lactation dairy cows

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
M. Vailati-Riboni ◽  
D. N. Coleman ◽  
V. Lopreiato ◽  
A. Alharthi ◽  
R. E. Bucktrout ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Somatic Cell ◽  
Pathway Analysis ◽  
Molecular Mechanisms ◽  
Somatic Cell Score ◽  
Molecular Networks ◽  
Epithelial Tissue ◽  
Udder Health ◽  
Streptococcus Uberis ◽  
Fermentation Product

Abstract Background We aimed to characterize the protective effects and the molecular mechanisms of action of a Saccharomyces cerevisiae fermentation product (NTK) in response to a mastitis challenge. Eighteen mid-lactation multiparous Holstein cows (n = 9/group) were fed the control diet (CON) or CON supplemented with 19 g/d NTK for 45 d (phase 1, P1) and then infected in the right rear quarter with 2500 CFU of Streptococcus uberis (phase 2, P2). After 36-h, mammary gland and liver biopsies were collected and antibiotic treatment started until the end of P2 (9 d post challenge). Cows were then followed until day 75 (phase 3, P3). Milk yield (MY) and dry matter intake (DMI) were recorded daily. Milk samples for somatic cell score were collected, and rectal and udder temperature, heart and respiration rate were recorded during the challenge period (P2) together with blood samples for metabolite and immune function analyses. Data were analyzed by phase using the PROC MIXED procedure in SAS. Biopsies were used for transcriptomic analysis via RNA-sequencing, followed by pathway analysis. Results DMI and MY were not affected by diet in P1, but an interaction with time was recorded in P2 indicating a better recovery from the challenge in NTK compared with CON. NTK reduced rectal temperature, somatic cell score, and temperature of the infected quarter during the challenge. Transcriptome data supported these findings, as NTK supplementation upregulated mammary genes related to immune cell antibacterial function (e.g., CATHL4, NOS2), epithelial tissue protection (e.g. IL17C), and anti-inflammatory activity (e.g., ATF3, BAG3, IER3, G-CSF, GRO1, ZFAND2A). Pathway analysis indicated upregulation of tumor necrosis factor α, heat shock protein response, and p21 related pathways in the response to mastitis in NTK cows. Other pathways for detoxification and cytoprotection functions along with the tight junction pathway were also upregulated in NTK-fed cows. Conclusions Overall, results highlighted molecular networks involved in the protective effect of NTK prophylactic supplementation on udder health during a subclinical mastitic event.

scholarly journals Capn4 Enhances Osteopontin Expression through Activation of the Wnt/β-Catenin Pathway to Promote Epithelial Ovarian Carcinoma Metastasis

2017 ◽  
Vol 42 (1) ◽  
pp. 185-197 ◽  
Author(s):  
Xiaoming Yang ◽  
Jing Sun ◽  
Dandan Xia ◽  
Xupei Can ◽  
Lei Liu ◽  
...  
Keyword(s):  
Ovarian Carcinoma ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Western Blotting ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Epithelial Ovarian Carcinoma ◽  
Regulatory Subunit ◽  
Epithelial Tissue

Background and Aim: Increasing evidence shows that the calpain regulatory subunit Capn4 can modulate the proliferation and metastasis of cancer cells, and plays an important role in the development of malignant tumors. However, there is no information on the clinical significance of Capn4 in epithelial ovarian carcinoma (EOC) or the molecular mechanisms by which Capn4 promotes the growth and metastasis of EOC. Therefore, the aim of this study was to clarify the role of Capn4 in EOC. Methods: We evaluated Capn4 and osteopontin (OPN) expression in EOC cell lines and tissues from patients with ovarian cancer by western blotting and immunohistochemical analysis. We then created cell lines with downregulated and upregulated Capn4 expression, using Capn4-targeting small interfering RNA and a pcDNA3.1-Capn4 overexpression vector, respectively, to investigate its function in EOC in vitro. In addition, we investigated the potential mechanism underlying the function of Capn4 by examining the effect of modifying Capn4 expression on Wnt/β-catenin signaling pathway-related genes by western blotting. Results: Capn4 was overexpressed in clinical EOC tissues compared with that in normal ovarian epithelial tissue, and was associated with poor clinical outcomes. Upon silencing or overexpressing Capn4 in EOC cells, we concluded that Capn4 promotes cell proliferation and migration in vitro. Furthermore, Capn4 promoted EOC metastasis by interacting with the Wnt/β-catenin signaling pathway to upregulate OPN expression. Conclusion: Our study indicates that Capn4 plays a critical role in the progression and metastasis of EOC, and could be a potential therapeutic target for EOC management.

scholarly journals Discovery of keratin function and role in genetic diseases: the year that 1991 was

2016 ◽  
Vol 27 (18) ◽  
pp. 2807-2810 ◽  
Author(s):  
Pierre A. Coulombe
Keyword(s):  
Intermediate Filaments ◽  
Cell Biology ◽  
Essential Role ◽  
Genetic Diseases ◽  
Structure And Function ◽  
Mechanical Support ◽  
25Th Anniversary ◽  
Keratin Filaments ◽  
And Function ◽  
Keratin Intermediate Filaments

In 1991, a set of transgenic mouse studies took the fields of cell biology and dermatology by storm in providing the first credible evidence that keratin intermediate filaments play a unique and essential role in the structural and mechanical support in keratinocytes of the epidermis. Moreover, these studies intimated that mutations altering the primary structure and function of keratin filaments underlie genetic diseases typified by cellular fragility. This Retrospective on how these studies came to be is offered as a means to highlight the 25th anniversary of these discoveries.

Engrailed-1 and netrin-1 regulate axon pathfinding by association interneurons that project to motor neurons

Development ◽  
1999 ◽  
Vol 126 (19) ◽  
pp. 4201-4212 ◽  
Author(s):  
H. Saueressig ◽  
J. Burrill ◽  
M. Goulding
Keyword(s):  
Spinal Cord ◽  
Motor Neurons ◽  
Molecular Mechanisms ◽  
Axon Growth ◽  
Cell Types ◽  
Second Phase ◽  
Axon Pathfinding ◽  
Cell Type Specific ◽  
Embryonic Spinal Cord ◽  
Ventrolateral Funiculus

During early development, multiple classes of interneurons are generated in the spinal cord including association interneurons that synapse with motor neurons and regulate their activity. Very little is known about the molecular mechanisms that generate these interneuron cell types, nor is it known how axons from association interneurons are guided toward somatic motor neurons. By targeting the axonal reporter gene τ-lacZ to the En1 locus, we show the cell-type-specific transcription factor Engrailed-1 (EN1) defines a population of association neurons that project locally to somatic motor neurons. These EN1 interneurons are born early and their axons pioneer an ipsilateral longitudinal projection in the ventral spinal cord. The EN1 interneurons extend axons in a stereotypic manner, first ventrally, then rostrally for one to two segments where their axons terminate close to motor neurons. We show that the growth of EN1 axons along a ventrolateral pathway toward motor neurons is dependent on netrin-1 signaling. In addition, we demonstrate that En1 regulates pathfinding and fasciculation during the second phase of EN1 axon growth in the ventrolateral funiculus (VLF); however, En1 is not required for the early specification of ventral interneuron cell types in the embryonic spinal cord.

Structural Features of Keratin Intermediate Filaments

1988 ◽  
pp. 157-167 ◽  
Author(s):  
P. M. Steinert ◽  
D. R. Torchia ◽  
J. W. Mack
Keyword(s):  
Intermediate Filaments ◽  
Structural Features ◽  
Keratin Intermediate Filaments
Sign in / Sign up

Export Citation Format

Share Document