scholarly journals Excitable Signal Transduction Networks in Directed Cell Migration

2017 ◽  
Vol 33 (1) ◽  
pp. 103-125 ◽  
Author(s):  
Peter N. Devreotes ◽  
Sayak Bhattacharya ◽  
Marc Edwards ◽  
Pablo A. Iglesias ◽  
Thomas Lampert ◽  
...  
2019 ◽  
Vol 63 (8-9-10) ◽  
pp. 407-416 ◽  
Author(s):  
Dhiman S. Pal ◽  
Xiaoguang Li ◽  
Tatsat Banerjee ◽  
Yuchuan Miao ◽  
Peter N. Devreotes

In response to a variety of external cues, eukaryotic cells display varied migratory modes to perform their physiological functions during development and in the adult. Aberrations in cell migration result in embryonic defects and cancer metastasis. The molecular components involved in cell migration are remarkably conserved between the social amoeba Dictyostelium and mammalian cells. This makes the amoeba an excellent model system for studies of eukaryotic cell migration. These migration-associated components can be grouped into three networks: input, signal transduction and cytoskeletal. In migrating cells, signal transduction events such as Ras or PI3K activity occur at the protrusion tips, referred to as ‘front’, whereas events such as dissociation of PTEN from these regions are referred to as ‘back’. Asymmetric distribution of such front and back events is crucial for establishing polarity and guiding cell migration. The triggering of these signaling events displays properties of biochemical excitability including all-or-nothing responsiveness to suprathreshold stimuli, refractoriness, and wave propagation. These signal transduction waves originate from a point and propagate towards the edge of the cell, thereby driving cytoskeletal activity and cellular protrusions. Any change in the threshold for network activation alters the range of the propagating waves and the size of cellular protrusions which gives rise to various migratory modes in cells. Thus, this review highlights excitable signal transduction networks as key players for coordinating cytoskeletal activities to drive cell migration in all eukaryotes.


2021 ◽  
Vol 120 (3) ◽  
pp. 112a-113a
Author(s):  
Peter N. Devreotes ◽  
Tatsat Banerjee ◽  
Dhiman S. Pal ◽  
Debojyoti Biswas ◽  
Huiwang Zhan ◽  
...  

Development ◽  
2001 ◽  
Vol 128 (15) ◽  
pp. 3001-3015 ◽  
Author(s):  
Pamela L. Bradley ◽  
Deborah J. Andrew

During development, directed cell migration is crucial for achieving proper shape and function of organs. One well-studied example is the embryonic development of the larval tracheal system of Drosophila, in which at least four signaling pathways coordinate cell migration to form an elaborate branched network essential for oxygen delivery throughout the larva. FGF signaling is required for guided migration of all tracheal branches, whereas the DPP, EGF receptor, and Wingless/WNT signaling pathways each mediate the formation of specific subsets of branches. Here, we characterize ribbon, which encodes a BTB/POZ-containing protein required for specific tracheal branch migration. In ribbon mutant tracheae, the dorsal trunk fails to form, and ventral branches are stunted; however, directed migrations of the dorsal and visceral branches are largely unaffected. The dorsal trunk also fails to form when FGF or Wingless/WNT signaling is lost, and we show that ribbon functions downstream of, or parallel to, these pathways to promote anterior-posterior migration. Directed cell migration of the salivary gland and dorsal epidermis are also affected in ribbon mutants, suggesting that conserved mechanisms may be employed to orient cell migrations in multiple tissues during development.


2017 ◽  
Vol 352 (2) ◽  
pp. 255-264 ◽  
Author(s):  
Magdalena Blom ◽  
Katarina Reis ◽  
Johan Heldin ◽  
Johan Kreuger ◽  
Pontus Aspenström

2009 ◽  
Vol 20 (22) ◽  
pp. 4706-4719 ◽  
Author(s):  
Jianxin A. Yu ◽  
Nicholas O. Deakin ◽  
Christopher E. Turner

Directed cell migration requires the coordination of growth factor and cell adhesion signaling and is of fundamental importance during embryonic development, wound repair, and pathological conditions such as tumor metastasis. Herein, we demonstrate that the ArfGAP, paxillin-kinase-linker (PKL/GIT2), is tyrosine phosphorylated in response to platelet-derived growth factor (PDGF) stimulation, in an adhesion dependent manner and is necessary for directed cell migration. Using a combination of pharmacological inhibitors, knockout cells and kinase mutants, FAK, and Src family kinases were shown to mediate PDGF-dependent PKL tyrosine phosphorylation. In fibroblasts, expression of a PKL mutant lacking the principal tyrosine phosphorylation sites resulted in loss of wound-induced cell polarization as well as directional migration. PKL phosphorylation was necessary for PDGF-stimulated PKL binding to the focal adhesion protein paxillin and expression of paxillin or PKL mutants defective in their respective binding motifs recapitulated the polarization defects. RNA interference or expression of phosphorylation mutants of PKL resulted in disregulation of PDGF-stimulated Rac1 and PAK activities, reduction of Cdc42 and Erk signaling, as well as mislocalization of βPIX. Together these studies position PKL as an integral component of growth factor and cell adhesion cross-talk signaling, controlling the development of front–rear cell polarity and directional cell migration.


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