scholarly journals NBR1 enables autophagy-dependent focal adhesion turnover

2016 ◽  
Vol 212 (5) ◽  
pp. 577-590 ◽  
Author(s):  
Candia M. Kenific ◽  
Samantha J. Stehbens ◽  
Juliet Goldsmith ◽  
Andrew M. Leidal ◽  
Nathalie Faure ◽  
...  
Keyword(s):  
Membrane Vesicle ◽  
Ectopic Expression ◽  
Focal Adhesions ◽  
Selective Autophagy ◽  
Cell Matrix ◽  
Motile Cells ◽  
Dynamic Assembly ◽  
Focal Adhesion Turnover ◽  
Underlying Mechanisms ◽  
Insight Into

Autophagy is a catabolic pathway involving the sequestration of cellular contents into a double-membrane vesicle, the autophagosome. Although recent studies have demonstrated that autophagy supports cell migration, the underlying mechanisms remain unknown. Using live-cell imaging, we uncover that autophagy promotes optimal migratory rate and facilitates the dynamic assembly and disassembly of cell-matrix focal adhesions (FAs), which is essential for efficient motility. Additionally, our studies reveal that autophagosomes associate with FAs primarily during disassembly, suggesting autophagy locally facilitates the destabilization of cell-matrix contact sites. Furthermore, we identify the selective autophagy cargo receptor neighbor of BRCA1 (NBR1) as a key mediator of autophagy-dependent FA remodeling. NBR1 depletion impairs FA turnover and decreases targeting of autophagosomes to FAs, whereas ectopic expression of autophagy-competent, but not autophagy-defective, NBR1 enhances FA disassembly and reduces FA lifetime during migration. Our findings provide mechanistic insight into how autophagy promotes migration by revealing a requirement for NBR1-mediated selective autophagy in enabling FA disassembly in motile cells.

scholarly journals Ca2+/H+ exchange by acidic organelles regulates cell migration in vivo

2016 ◽  
Vol 212 (7) ◽  
pp. 803-813 ◽  
Author(s):  
Manuela Melchionda ◽  
Jon K. Pittman ◽  
Roberto Mayor ◽  
Sandip Patel
Keyword(s):  
Cell Migration ◽  
Neural Crest ◽  
Cell Matrix ◽  
Physiological Relevance ◽  
Underlying Mechanisms ◽  
Acidic Organelles ◽  
Cell Matrix Adhesion ◽  
Insight Into

Increasing evidence implicates Ca2+ in the control of cell migration. However, the underlying mechanisms are incompletely understood. Acidic Ca2+ stores are fast emerging as signaling centers. But how Ca2+ is taken up by these organelles in metazoans and the physiological relevance for migration is unclear. Here, we identify a vertebrate Ca2+/H+ exchanger (CAX) as part of a widespread family of homologues in animals. CAX is expressed in neural crest cells and required for their migration in vivo. It localizes to acidic organelles, tempers evoked Ca2+ signals, and regulates cell-matrix adhesion during migration. Our data provide new molecular insight into how Ca2+ is handled by acidic organelles and link this to migration, thereby underscoring the role of noncanonical Ca2+ stores in the control of Ca2+-dependent function.

scholarly journals Microtubule acetylation but not detyrosination promotes focal adhesion dynamics and cell migration

2018 ◽  
Author(s):  
Bertille Bance ◽  
Shailaja Seetharaman ◽  
Cécile Leduc ◽  
Batiste Boëda ◽  
Sandrine Etienne-Manneville
Keyword(s):  
Cell Migration ◽  
Focal Adhesion ◽  
Focal Adhesions ◽  
Cell Polarization ◽  
Post Translational Modifications ◽  
Tubulin Acetylation ◽  
Focal Adhesion Turnover ◽  
Regulatory Functions ◽  
Insight Into

AbstractMicrotubules play a crucial role in mesenchymal migration by controlling cell polarity and the turnover of cell adhesive structures on the extracellular matrix. The polarized functions of microtubules imply that microtubules are locally regulated. Here, we investigated the regulation and role of two major tubulin post-translational modifications, acetylation and detyrosination, which have been associated with stable microtubules. Using primary astrocytes in a wound healing assay, we show that these tubulin modifications are independently regulated during cell polarization and differently affect cell migration. In contrast to microtubule detyrosination, αTAT1-mediated microtubule acetylation increases in the vicinity of focal adhesions and promotes cell migration. We further demonstrate that αTAT1 increases focal adhesion turnover by promoting Rab6-positive vesicle fusion at focal adhesions. Our results highlight the specificity of microtubule post-translational modifications and bring new insight into the regulatory functions of tubulin acetylation.

scholarly journals Structural Insight into the Mechanisms of Targeting and Signaling of Focal Adhesion Kinase

2002 ◽  
Vol 22 (8) ◽  
pp. 2751-2760 ◽  
Author(s):  
Gaohua Liu ◽  
Cristina D. Guibao ◽  
Jie Zheng
Keyword(s):  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Solution Structure ◽  
Hydrophobic Interactions ◽  
Focal Adhesions ◽  
Nonreceptor Tyrosine Kinase ◽  
Binding Partner ◽  
Focal Adhesion Turnover ◽  
Structural Insight ◽  
Insight Into

ABSTRACT Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase whose focal adhesion targeting (FAT) domain interacts with other focal adhesion molecules in integrin-mediated signaling. Localization of activated FAK to focal adhesions is indispensable for its function. Here we describe a solution structure of the FAT domain bound to a peptide derived from paxillin, a FAK-binding partner. The FAT domain is composed of four helices that form a “right-turn” elongated bundle; the globular fold is mainly maintained by hydrophobic interactions. The bound peptide further stabilizes the structure. Certain signaling events such as phosphorylation and molecule interplay may induce opening of the helix bundle. Such conformational change is proposed to precede departure of FAK from focal adhesions, which starts focal adhesion turnover.

scholarly journals Gut Microbiome and Metabolome Profiles Associated with High-Fat Diet in Mice

Metabolites ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 482
Author(s):  
Jae-Kwon Jo ◽  
Seung-Ho Seo ◽  
Seong-Eun Park ◽  
Hyun-Woo Kim ◽  
Eun-Ju Kim ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Relative Abundance ◽  
High Fat Diet ◽  
Amplicon Sequencing ◽  
Gas Chromatography Mass Spectrometry ◽  
Control Group ◽  
Rrna Gene ◽  
High Fat ◽  
Underlying Mechanisms ◽  
Insight Into

Obesity can be caused by microbes producing metabolites; it is thus important to determine the correlation between gut microbes and metabolites. This study aimed to identify gut microbiota-metabolomic signatures that change with a high-fat diet and understand the underlying mechanisms. To investigate the profiles of the gut microbiota and metabolites that changed after a 60% fat diet for 8 weeks, 16S rRNA gene amplicon sequencing and gas chromatography-mass spectrometry (GC-MS)-based metabolomic analyses were performed. Mice belonging to the HFD group showed a significant decrease in the relative abundance of Bacteroidetes but an increase in the relative abundance of Firmicutes compared to the control group. The relative abundance of Firmicutes, such as Lactococcus, Blautia, Lachnoclostridium, Oscillibacter, Ruminiclostridium, Harryflintia, Lactobacillus, Oscillospira, and Erysipelatoclostridium, was significantly higher in the HFD group than in the control group. The increased relative abundance of Firmicutes in the HFD group was positively correlated with fecal ribose, hypoxanthine, fructose, glycolic acid, ornithine, serum inositol, tyrosine, and glycine. Metabolic pathways affected by a high fat diet on serum were involved in aminoacyl-tRNA biosynthesis, glycine, serine and threonine metabolism, cysteine and methionine metabolism, glyoxylate and dicarboxylate metabolism, and phenylalanine, tyrosine, and trypto-phan biosynthesis. This study provides insight into the dysbiosis of gut microbiota and metabolites altered by HFD and may help to understand the mechanisms underlying obesity mediated by gut microbiota.

scholarly journals Fibronectin has a dual role in locomotion and anchorage of primary chick fibroblasts and can promote entry into the division cycle.

1982 ◽  
Vol 93 (2) ◽  
pp. 402-410 ◽  
Author(s):  
J R Couchman ◽  
D A Rees ◽  
M R Green ◽  
C G Smith
Keyword(s):  
Focal Adhesion ◽  
Focal Adhesions ◽  
Growth Cycle ◽  
Culture Conditions ◽  
Biological Functions ◽  
Macromolecular Synthesis ◽  
Natural Factor ◽  
Motile Cells ◽  
Chick Heart ◽  
Gold Marker

Fibronectin (FN), which is already known to be a natural factor for fibroblast spreading on substrata, has now been shown to be essential for two distinct types of adhesion with different biological functions in chick heart fibroblasts, namely adhesion directed toward locomotion and toward stationary anchorage for growth. Manipulation of culture conditions and the use of antisera of differing specificities has demonstrated that both exogenous and cell-derived FN are important in each process. The organization of the fibronectin-containing matrix differs between the two states. Immunoelectron microscopy with a colloidal gold marker reveals the presence of small membrane-associated plaques of fibronectin in motile cells with associated submembranous specialization. A fibrillar matrix containing fibronectin is dominant in nonmotile, growing fibroblasts. The development of focal adhesions for stationary anchorage can be dramatically enhanced by addition of cell-derived FN at an appropriate stage, and this promotes entry into the growth cycle. New macromolecular synthesis in addition to FN is necessary for focal adhesion development but not for locomotion.

Nominal Number and Language Pathologies

2021 ◽  
pp. 290-304
Author(s):  
Britta Biedermann ◽  
Nora Fieder ◽  
Karen Smith-Lock
Keyword(s):  
Language Impairment ◽  
Language Production ◽  
Developmental Delays ◽  
Language Disorder ◽  
Number Processing ◽  
Developmental Language Disorder ◽  
Cognitive Neuropsychology ◽  
Underlying Mechanisms ◽  
Grammatical Number ◽  
Insight Into

This chapter provides an overview of the evidence on grammatical number processing taken from cognitive neuropsychology, including developmental delays and impairments of language (e.g. developmental language disorder, and Williams syndrome) and aphasia, an acquired language impairment after brain injury. These types of language impairment can give insight into the functional architecture of nominal number processing by looking at error patterns that arise in each of the aforementioned populations. By classifying observed responses in language production tasks into non-number and number errors, we are able to reveal underlying mechanisms of syntactic rules and their representations when they develop, but also learn about processes and representation of number when this information breaks down.

scholarly journals Lipid rafts mediate internalization of β1-integrin in migrating intestinal epithelial cells

2008 ◽  
Vol 295 (5) ◽  
pp. G965-G976 ◽  
Author(s):  
Elena V. Vassilieva ◽  
Kirsten Gerner-Smidt ◽  
Andrei I. Ivanov ◽  
Asma Nusrat
Keyword(s):  
Epithelial Cells ◽  
Lipid Rafts ◽  
Lipid Raft ◽  
Intestinal Epithelial Cells ◽  
Focal Adhesions ◽  
Endocytic Pathway ◽  
Dependent Manner ◽  
Intestinal Epithelial ◽  
Caveolin 1 ◽  
Cell Matrix

Intestinal mucosal inflammation is associated with epithelial wounds that rapidly reseal by migration of intestinal epithelial cells (IECs). Cell migration involves cycles of cell-matrix adhesion/deadhesion that is mediated by dynamic turnover (assembly and disassembly) of integrin-based focal adhesions. Integrin endocytosis appears to be critical for deadhesion of motile cells. However, mechanisms of integrin internalization during remodeling of focal adhesions of migrating IECs are not understood. This study was designed to define the endocytic pathway that mediates internalization of β1-integrin in migrating model IECs. We observed that, in SK-CO15 and T84 colonic epithelial cells, β1-integrin is internalized in a dynamin-dependent manner. Pharmacological inhibition of clathrin-mediated endocytosis or macropinocytosis and small-interfering RNA (siRNA)-mediated knock down of clathrin did not prevent β1-integrin internalization. However, β1-integrin internalization was inhibited following cholesterol extraction and after overexpression of lipid raft protein, caveolin-1. Furthermore, internalized β1-integrin colocalized with the lipid rafts marker cholera toxin, and siRNA-mediated knockdown of caveolin-1 and flotillin-1/2 increased β1-integrin endocytosis. Our data suggest that, in migrating IEC, β1-integrin is internalized via a dynamin-dependent lipid raft-mediated pathway. Such endocytosis is likely to be important for disassembly of integrin-based cell-matrix adhesions and therefore in regulating IEC migration and wound closure.

scholarly journals Dislocation–grain boundary interactions: recent advances on the underlying mechanisms studied via nanoindentation testing

2021 ◽  
Author(s):  
Farhan Javaid ◽  
Habib Pouriayevali ◽  
Karsten Durst
Keyword(s):  
Grain Boundary ◽  
Mechanical Response ◽  
Displacement Curve ◽  
Ambient Conditions ◽  
Recent Advances ◽  
Slip Transfer ◽  
Depth Analysis ◽  
Dislocation Interactions ◽  
Underlying Mechanisms ◽  
Insight Into

Abstract To comprehend the mechanical behavior of a polycrystalline material, an in-depth analysis of individual grain boundary (GB) and dislocation interactions is of prime importance. In the past decade, nanoindentation emerged as a powerful tool to study the local mechanical response in the vicinity of the GB. The improved instrumentation and test protocols allow to capture various GB–dislocation interactions during the nanoindentation in the form of strain bursts on the load–displacement curve. Moreover, the interaction of the plastic zone with the GB provides important insight into the dislocation transmission effects of distinct grain boundaries. Of great importance for the analysis and interpretation of the observed effects are microstructural investigations and computational approaches. This review paper focused on recent advances in the dislocation–GB interactions and underlying mechanisms studied via nanoindentation, which includes GB pop-in phenomenon, localized grain movement under ambient conditions, and an analysis of the slip transfer mechanism using theoretical treatments and simulations. Graphical abstract

scholarly journals Phosphoinositides regulate force-independent interactions between talin, vinculin, and actin

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Charlotte F Kelley ◽  
Thomas Litschel ◽  
Stephanie Schumacher ◽  
Dirk Dedden ◽  
Petra Schwille ◽  
...  
Keyword(s):  
Network Formation ◽  
Focal Adhesions ◽  
Membrane Composition ◽  
Macromolecular Assemblies ◽  
In Vitro Reconstitution ◽  
Membrane Bound ◽  
Underlying Mechanisms ◽  
Higher Order Networks ◽  
Made In

Focal adhesions (FA) are large macromolecular assemblies which help transmit mechanical forces and regulatory signals between the extracellular matrix and an interacting cell. Two key proteins talin and vinculin connecting integrin to actomyosin networks in the cell. Both proteins bind to F-actin and each other, providing a foundation for network formation within FAs. However, the underlying mechanisms regulating their engagement remain unclear. Here, we report on the results of in vitro reconstitution of talin-vinculin-actin assemblies using synthetic membrane systems. We find that neither talin nor vinculin alone recruit actin filaments to the membrane. In contrast, phosphoinositide-rich membranes recruit and activate talin, and the membrane-bound talin then activates vinculin. Together, the two proteins then link actin to the membrane. Encapsulation of these components within vesicles reorganized actin into higher-order networks. Notably, these observations were made in the absence of applied force, whereby we infer that the initial assembly stage of FAs is force independent. Our findings demonstrate that the local membrane composition plays a key role in controlling the stepwise recruitment, activation, and engagement of proteins within FAs.

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