scholarly journals Distinct Recruitment and Function of Gab1 and Gab2 in Met Receptor-mediated Epithelial Morphogenesis

2002 ◽  
Vol 13 (6) ◽  
pp. 2132-2146 ◽  
Author(s):  
Lisa S. Lock ◽  
Christiane R. Maroun ◽  
Monica A. Naujokas ◽  
Morag Park
Keyword(s):  
Epithelial Cells ◽  
Epithelial Morphogenesis ◽  
Cell Junctions ◽  
Signaling Proteins ◽  
Met Receptor ◽  
Morphogenic Response ◽  
Docking Proteins ◽  
And Function ◽  
Multiple Signaling

The Gab family of docking proteins (Gab1 and Gab2) are phosphorylated in response to various cytokines and growth factors. Gab1 acts to diversify the signal downstream from the Met receptor tyrosine kinase through the recruitment of multiple signaling proteins, and is essential for epithelial morphogenesis. To determine whether Gab1 and Gab2 are functionally redundant, we have examined the role of Gab2 in epithelial cells. Both Gab1 and Gab2 are expressed in epithelial cells and localize to cell-cell junctions. However, whereas overexpression of Gab1 promotes a morphogenic response, the overexpression of Gab2 fails to induce this response. We show that Gab2 recruitment to the Met receptor is dependent on the Grb2 adapter protein. In contrast, Gab1 recruitment to Met is both Grb2 dependent and Grb2 independent. The latter requires a novel amino acid sequence present in the Met-binding domain of Gab1 but not Gab2. Mutation of these residues in Gab1 impairs both association with the Met receptor and the ability of Gab1 to promote a morphogenic response, whereas their insertion into Gab2 increases Gab2 association with Met, but does not confer on Gab2 the ability to promote epithelial morphogenesis. We propose that the Grb2-independent recruitment of Gab proteins to Met is necessary but not sufficient to promote epithelial morphogenesis.

scholarly journals Critical role of histone H3 lysine 27 demethylase Kdm6b in the homeostasis and function of medullary thymic epithelial cells

2020 ◽  
Vol 27 (10) ◽  
pp. 2843-2855
Author(s):  
Zhi Liu ◽  
Haohao Zhang ◽  
Yiming Hu ◽  
Dandan Liu ◽  
Lingling Li ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Critical Role ◽  
Histone H3 ◽  
Thymic Epithelial Cells ◽  
Medullary Thymic Epithelial Cells ◽  
And Function

scholarly journals Deciliation Is Associated with Dramatic Remodeling of Epithelial Cell Junctions and Surface Domains

2009 ◽  
Vol 20 (1) ◽  
pp. 102-113 ◽  
Author(s):  
Christian E. Overgaard ◽  
Kaitlin M. Sanzone ◽  
Krystle S. Spiczka ◽  
David R. Sheff ◽  
Alexander Sandra ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Primary Cilia ◽  
Mdck Cells ◽  
Cell Junctions ◽  
Apical Trafficking ◽  
Epithelial Remodeling ◽  
Surface Domains ◽  
And Function ◽  
Mediated Reduction ◽  
Junction Proteins

Stress-induced shedding of motile cilia (autotomy) has been documented in diverse organisms and likely represents a conserved cellular reaction. However, little is known about whether primary cilia are shed from mammalian epithelial cells and what impact deciliation has on polarized cellular organization. We show that several chemically distinct agents trigger autotomy in epithelial cells. Surprisingly, deciliation is associated with a significant, but reversible increase in transepithelial resistance. This reflects substantial reductions in tight junction proteins associated with “leaky” nephron segments (e.g., claudin-2). At the same time, apical trafficking of gp80/clusterin and gp114/CEACAM becomes randomized, basal-lateral delivery of Na,K-ATPase is reduced, and expression of the nonciliary apical protein gp135/podocalyxin is greatly decreased. However, ciliogenesis-impaired MDCK cells do not undergo continual junction remodeling, and mature cilia are not required for autotomy-associated remodeling events. Deciliation and epithelial remodeling may be mechanistically linked processes, because RNAi-mediated reduction of Exocyst subunit Sec6 inhibits ciliary shedding and specifically blocks deciliation-associated down-regulation of claudin-2 and gp135. We propose that ciliary autotomy represents a signaling pathway that impacts the organization and function of polarized epithelial cells.

scholarly journals SFPQ Rescues F508del-CFTR Expression and Function in Cystic Fibrosis Bronchial Epithelial Cells

2021 ◽  
Author(s):  
Parameet Kumar ◽  
Dharmendra Kumar Soni ◽  
Chaitali Sen ◽  
Mads B Larsen ◽  
Krystyna Mazan-Mamczarz ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Cells ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Regulation Of Gene Expression ◽  
Lung Epithelial Cells ◽  
Regulation Of Expression ◽  
Trafficking Defects ◽  
And Function

Abstract Cystic Fibrosis (CF) occurs as a result of mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which lead to misfolding, trafficking defects, and impaired function of the CFTR protein. Splicing factor proline/glutamine-rich (SFPQ) is a multifunctional nuclear RNA-binding protein (RBP) implicated in the regulation of gene expression pathways and intracellular trafficking. Here, we investigated the role of SFPQ in the regulation of the expression and function of F508del-CFTR in CF lung epithelial cells. We find that the expression of SFPQ is reduced in F508del-CFTR CF epithelial cells compared to WT-CFTR control cells. Interestingly, the overexpression of SFPQ in CF cells increases the expression as well as rescues the function of F508del-CFTR. Further, comprehensive transcriptome analyses indicate that SFPQ plays a key role in activating the mutant F508del-CFTR by modulating several cellular signaling pathways. This is the first report on the role of SFPQ in the regulation of expression and function of F508del-CFTR in CF lung disease. Our findings provide new insights into SFPQ-mediated molecular mechanisms and point to possible novel epigenetic therapeutic targets for CF and related pulmonary diseases.

scholarly journals Comprehensive analysis of formin localization in Xenopus epithelial cells

2019 ◽  
Vol 30 (1) ◽  
pp. 82-95 ◽  
Author(s):  
Tomohito Higashi ◽  
Rachel E. Stephenson ◽  
Ann L. Miller
Keyword(s):  
Epithelial Cells ◽  
Comprehensive Analysis ◽  
Cell Junctions ◽  
Actin Dynamics ◽  
Cell Junction ◽  
Contractile Ring ◽  
Dimerization Domain ◽  
Cellular Processes ◽  
And Function ◽  
Cell Cell

Reorganization of the actin cytoskeleton is crucial for cellular processes, including cytokinesis and cell–cell junction remodeling. Formins are conserved processive actin-polymerizing machines that regulate actin dynamics by nucleating, elongating, and bundling linear actin filaments. Because the formin family is large, with at least 15 members in vertebrates, there have not been any comprehensive studies examining formin localization and function within a common cell type. Here, we characterized the localization of all 15 formins in epithelial cells of Xenopus laevis gastrula-stage embryos. Dia1 and Dia2 localized to tight junctions, while Fhod1 and Fhod3 localized to adherens junctions. Only Dia3 strongly localized at the cytokinetic contractile ring. The Diaphanous inhibitory domain–dimerization domain (DID-DD) region of Dia1 was sufficient for Dia1 localization, and overexpression of a Dia1 DID-DD fragment competitively removed Dia1 and Dia2 from cell–cell junctions. In Dia1 DID-DD–overexpressing cells, Dia1 and Dia2 were mislocalized to the contractile ring, and cells exhibited increased cytokinesis failure. This work provides a comprehensive analysis of the localization of all 15 vertebrate formins in epithelial cells and suggests that misregulated formin localization results in epithelial cytokinesis failure.

scholarly journals Targeted Ptpn11 deletion in mice reveals the essential role of SHP2 in osteoblast differentiation and skeletal homeostasis

Bone Research ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Lijun Wang ◽  
Huiliang Yang ◽  
Jiahui Huang ◽  
Shaopeng Pei ◽  
Liyun Wang ◽  
...  
Keyword(s):  
Bone Cells ◽  
Protein Tyrosine Phosphatases ◽  
Osteoblastic Differentiation ◽  
Bone Cell ◽  
Signaling Proteins ◽  
Tubular Bone ◽  
Skeletal Homeostasis ◽  
Underlying Mechanisms ◽  
And Function

AbstractThe maturation and function of osteoblasts (OBs) rely heavily on the reversible phosphorylation of signaling proteins. To date, most of the work in OBs has focused on phosphorylation by tyrosyl kinases, but little has been revealed about dephosphorylation by protein tyrosine phosphatases (PTPases). SHP2 (encoded by PTPN11) is a ubiquitously expressed PTPase. PTPN11 mutations are associated with both bone and cartilage manifestations in patients with Noonan syndrome (NS) and metachondromatosis (MC), although the underlying mechanisms remain elusive. Here, we report that SHP2 deletion in bone gamma-carboxyglutamate protein-expressing (Bglap+) bone cells leads to massive osteopenia in both trabecular and cortical bones due to the failure of bone cell maturation and enhanced osteoclast activity, and its deletion in Bglap+ chondrocytes results in the onset of enchondroma and osteochondroma in aged mice with increased tubular bone length. Mechanistically, SHP2 was found to be required for osteoblastic differentiation by promoting RUNX2/OSTERIX signaling and for the suppression of osteoclastogenesis by inhibiting STAT3-mediated RANKL production by osteoblasts and osteocytes. These findings are likely to explain the compromised skeletal system in NS and MC patients and to inform the development of novel therapeutics to combat skeletal disorders.

scholarly journals Overview of Research Development on the Role of NF-κB Signaling in Mastitis

Animals ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1625
Author(s):  
Muhammad Zahoor Khan ◽  
Adnan Khan ◽  
Jianxin Xiao ◽  
Jiaying Ma ◽  
Yulin Ma ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Mammary Epithelial Cells ◽  
Inflammatory Diseases ◽  
Control Strategies ◽  
Nuclear Factor Κb ◽  
Mammary Epithelial ◽  
And Function ◽  
And Staphylococcus Aureus ◽  
Mastitis Control

Mastitis is the inflammation of the mammary gland. Escherichia coli and Staphylococcus aureus are the most common bacteria responsible for mastitis. When mammary epithelial cells are infected by microorganisms, this activates an inflammatory response. The bacterial infection is recognized by innate pattern recognition receptors (PRRs) in the mammary epithelial cells, with the help of Toll-like receptors (TLRs). Upon activation by lipopolysaccharides, a virulent agent of bacteria, the TLRs further trigger nuclear factor-κB (NF-κB) signaling to accelerate its pathogenesis. The NF-κB has an essential role in many biological processes, such as cell survival, immune response, inflammation and development. Therefore, the NF-κB signaling triggered by the TLRs then regulates the transcriptional expression of specific inflammatory mediators to initiate inflammation of the mammary epithelial cells. Thus, any aberrant regulation of NF-κB signaling may lead to many inflammatory diseases, including mastitis. Hence, the inhibiting of NF-κB signaling has potential therapeutic applications in mastitis control strategies. In this review, we highlighted the regulation and function of NF-κB signaling in mastitis. Furthermore, the role of NF-κB signaling for therapeutic purposes in mastitis control has been explored in the current review.

Cytokinesis and the establishment of early embryonic cell polarity

2008 ◽  
Vol 36 (3) ◽  
pp. 384-386 ◽  
Author(s):  
David R. Burgess
Keyword(s):  
Epithelial Cells ◽  
Cell Polarity ◽  
Primary Cilia ◽  
Embryonic Cell ◽  
Cell Junctions ◽  
Cell Contact ◽  
Apical Surface ◽  
Integral Role ◽  
Cell Cell

Cleavage divisions in many animals form a blastula made up of a simple polarized epithelium. This simple embryonic epithelium possesses an apical surface covered with microvilli and primary cilia separated from the basolateral surfaces by cell–cell junctions. The apical membrane proteins and lipids differ from those of the basolateral on these embryonic epithelial cells, as is found in adult epithelial cells. Formation of cell polarity in embryos at fertilization, including those from both protostomes and deuterostomes, uses the same molecules and signalling machinery as do polarizing epithelial cells that polarize upon cell–cell contact. In addition, the actin–myosin cytoskeleton plays an integral role in establishment and maintenance of this early cell polarity. However, early cleaving blastomeres from higher organisms including echinoderms and vertebrates have not been considered to exhibit cell polarity until formation of junctions at the third through to the fifth cleavage divisions. The role of new membrane addition into the late cleavage furrow during the early rounds of cytokinesis may play a key role in the early establishment of cell polarity in all animal embryos.

Sign in / Sign up

Export Citation Format

Share Document