Functional Analysis of FAK and Associated Molecules in Cell Migration

Author(s):  
Leslie Cary ◽  
Jun-Lin Guan
2011 ◽  
Vol 193 (1) ◽  
pp. 61-70 ◽  
Author(s):  
Zhizhan Gu ◽  
Erika H. Noss ◽  
Victor W. Hsu ◽  
Michael B. Brenner

During cell migration, integrins are redistributed from focal adhesions undergoing disassembly at the cell’s trailing edges to new focal adhesions assembling at leading edges. The initial step of integrin redistribution is thought to require clathrin-mediated endocytosis. However, whether clathrin-mediated endocytosis functions in different contexts, such as basal versus stimulated migration, has not been determined. In this paper, we examine the spatial and temporal redistribution of integrins from focal adhesions upon stimulation by growth factors. Four-dimensional confocal live-cell imaging along with functional analysis reveals that surface integrins do not undergo significant endocytosis at ventral focal adhesions upon cell stimulation with the platelet-derived growth factor. Rather, they abruptly redistribute to dorsal circular ruffles, where they are internalized through macropinocytosis. The internalized integrins then transit through recycling endosomal compartments to repopulate newly formed focal adhesions on the ventral surface. These findings explain why integrins have long been observed to redistribute through both surface-based and internal routes and identify a new function for macropinocytosis during growth factor–induced cell migration.


2017 ◽  
Vol 10 (499) ◽  
pp. eaal2987 ◽  
Author(s):  
Steven P. Williams ◽  
Adam F. Odell ◽  
Tara Karnezis ◽  
Rae H. Farnsworth ◽  
Cathryn M. Gould ◽  
...  

Author(s):  
Toshihiro Kushibiki ◽  
Hideo Eda ◽  
Tomoko Sano ◽  
Kunio Awazu

2015 ◽  
Vol 244 (8) ◽  
pp. 988-1013 ◽  
Author(s):  
Guillermo A. Vega-López ◽  
Marcela Bonano ◽  
Celeste Tríbulo ◽  
Juan P. Fernández ◽  
Tristán H. Agüero ◽  
...  

2012 ◽  
Vol 199 (3) ◽  
pp. 481-496 ◽  
Author(s):  
Emmanuel Dornier ◽  
Franck Coumailleau ◽  
Jean-François Ottavi ◽  
Julien Moretti ◽  
Claude Boucheix ◽  
...  

The metalloprotease ADAM10/Kuzbanian catalyzes the ligand-dependent ectodomain shedding of Notch receptors and activates Notch. Here, we show that the human tetraspanins of the evolutionary conserved TspanC8 subfamily (Tspan5, Tspan10, Tspan14, Tspan15, Tspan17, and Tspan33) directly interact with ADAM10, regulate its exit from the endoplasmic reticulum, and that four of them regulate ADAM10 surface expression levels. In an independent RNAi screen in Drosophila, two TspanC8 genes were identified as Notch regulators. Functional analysis of the three Drosophila TspanC8 genes (Tsp3A, Tsp86D, and Tsp26D) indicated that these genes act redundantly to promote Notch signaling. During oogenesis, TspanC8 genes were up-regulated in border cells and regulated Kuzbanian distribution, Notch activity, and cell migration. Furthermore, the human TspanC8 tetraspanins Tspan5 and Tspan14 positively regulated ligand-induced ADAM10-dependent Notch1 signaling. We conclude that TspanC8 tetraspanins have a conserved function in the regulation of ADAM10 trafficking and activity, thereby positively regulating Notch receptor activation.


2013 ◽  
Vol 42 (3) ◽  
pp. 873-880 ◽  
Author(s):  
MICHIYO YAMAMURA ◽  
KAZUMA NOGUCHI ◽  
YOSHIRO NAKANO ◽  
EMI SEGAWA ◽  
YUSUKE ZUSHI ◽  
...  

Author(s):  
J. Roemer ◽  
S.R. Simon

We are developing an in vitro interstitial extracellular matrix (ECM) system for study of inflammatory cell migration. Falcon brand Cyclopore membrane inserts of various pore sizes are used as a support substrate for production of ECM by R22 rat aortic smooth muscle cells. Under specific culture conditions these cells produce a highly insoluble matrix consisting of typical interstitial ECM components, i.e.: types I and III collagen, elastin, proteoglycans and fibronectin.


2019 ◽  
Vol 63 (5) ◽  
pp. 579-594 ◽  
Author(s):  
Guillem Lambies ◽  
Antonio García de Herreros ◽  
Víctor M. Díaz

Abstract Cell migration is a multifactorial/multistep process that requires the concerted action of growth and transcriptional factors, motor proteins, extracellular matrix remodeling and proteases. In this review, we focus on the role of transcription factors modulating Epithelial-to-Mesenchymal Transition (EMT-TFs), a fundamental process supporting both physiological and pathological cell migration. These EMT-TFs (Snail1/2, Twist1/2 and Zeb1/2) are labile proteins which should be stabilized to initiate EMT and provide full migratory and invasive properties. We present here a family of enzymes, the deubiquitinases (DUBs) which have a crucial role in counteracting polyubiquitination and proteasomal degradation of EMT-TFs after their induction by TGFβ, inflammatory cytokines and hypoxia. We also describe the DUBs promoting the stabilization of Smads, TGFβ receptors and other key proteins involved in transduction pathways controlling EMT.


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