scholarly journals Phosphorylation of WAVE2 by MAP kinases regulates persistent cell migration and polarity

2007 ◽  
Vol 120 (23) ◽  
pp. 4144-4154 ◽  
Author(s):  
C. M. Danson ◽  
S. M. Pocha ◽  
G. B. Bloomberg ◽  
G. O. Cory
Keyword(s):  
Cell Migration ◽  
Map Kinases ◽  
Persistent Cell

scholarly journals αvβ3 and α5β1 integrin recycling pathways dictate downstream Rho kinase signaling to regulate persistent cell migration

2007 ◽  
Vol 177 (3) ◽  
pp. 515-525 ◽  
Author(s):  
Dominic P. White ◽  
Patrick T. Caswell ◽  
Jim C. Norman
Keyword(s):  
Cell Migration ◽  
Rho Kinase ◽  
Cell Movement ◽  
Αvβ3 Integrin ◽  
Protein Kinase D1 ◽  
Fibroblast Migration ◽  
Short Loop ◽  
Cell Front ◽  
Α5β1 Integrin ◽  
Persistent Cell

Accumulating evidence suggests that integrin recycling regulates cell migration. However, the lack of reagents to selectively target the trafficking of individual heterodimers, as opposed to endocytic transport as a whole, has made it difficult to define the contribution made by particular recycling pathways to directional cell movement. We show that autophosphorylation of protein kinase D1 (PKD1) at Ser916 is necessary for its association with αvβ3 integrin. Expression of PKD1916A or the use of mutants of β3 that do not bind to PKD1 selectively inhibits short-loop, Rab4-dependent recycling of αvβ3, and this suppresses the persistence of fibroblast migration. However, we report that short-loop recycling does not directly contribute to fibroblast migration by moving αvβ3 to the cell front, but by antagonizing α5β1 recycling, which, in turn, influences the cell's decision to migrate with persistence or to move randomly.

scholarly journals Random versus directionally persistent cell migration

2009 ◽  
Vol 10 (8) ◽  
pp. 538-549 ◽  
Author(s):  
Ryan J. Petrie ◽  
Andrew D. Doyle ◽  
Kenneth M. Yamada
Keyword(s):  
Cell Migration ◽  
Persistent Cell

scholarly journals A cryptic tubulin-binding domain links MEKK1 to curved tubulin protomers

2020 ◽  
Vol 117 (35) ◽  
pp. 21308-21318 ◽  
Author(s):  
Pavel Filipčík ◽  
Sharissa L. Latham ◽  
Antonia L. Cadell ◽  
Catherine L. Day ◽  
David R. Croucher ◽  
...  
Keyword(s):  
Cell Migration ◽  
Map Kinases ◽  
Leading Edge ◽  
Structural Features ◽  
Selective Enrichment ◽  
Microtubule Polymerization ◽  
Binding Interface ◽  
Protein Map ◽  
Tubulin Binding ◽  
Mitogen Activated Protein

The MEKK1 protein is a pivotal kinase activator of responses to cellular stress. Activation of MEKK1 can trigger various responses, including mitogen-activated protein (MAP) kinases, NF-κB signaling, or cell migration. Notably, MEKK1 activity is triggered by microtubule-targeting chemotherapies, among other stressors. Here we show that MEKK1 contains a previously unidentified tumor overexpressed gene (TOG) domain. The MEKK1 TOG domain binds to tubulin heterodimers—a canonical function of TOG domains—but is unusual in that it appears alone rather than as part of a multi-TOG array, and has structural features distinct from previously characterized TOG domains. MEKK1 TOG demonstrates a clear preference for binding curved tubulin heterodimers, which exist in soluble tubulin and at sites of microtubule polymerization and depolymerization. Mutations disrupting tubulin binding decrease microtubule density at the leading edge of polarized cells, suggesting that tubulin binding may play a role in MEKK1 activity at the cellular periphery. We also show that MEKK1 mutations at the tubulin-binding interface of the TOG domain recur in patient-derived tumor sequences, suggesting selective enrichment of tumor cells with disrupted MEKK1–microtubule association. Together, these findings provide a direct link between the MEKK1 protein and tubulin, which is likely to be relevant to cancer cell migration and response to microtubule-modulating therapies.

scholarly journals α4β1-Integrin regulates directionally persistent cell migration in response to shear flow stimulation

2008 ◽  
Vol 295 (1) ◽  
pp. C151-C159 ◽  
Author(s):  
Dustin A. Dikeman ◽  
Leslie A. Rivera Rosado ◽  
Troy A. Horn ◽  
Christina S. Alves ◽  
Konstantinos Konstantopoulos ◽  
...  
Keyword(s):  
Cell Migration ◽  
Shear Flow ◽  
Complex Mechanism ◽  
Double Mutation ◽  
Trailing Edges ◽  
Flow Stimulation ◽  
Necessary And Sufficient ◽  
Persistent Cell ◽  
Insight Into

α4β1-Integrin plays a pivotal role in cell migration in vivo. This integrin has been shown to regulate the front-back polarity of migrating cells via localized inhibition of α4-integrin/paxillin binding by phosphorylation at the α4-integrin cytoplasmic tail. Here, we demonstrate that α4β1-integrin regulates directionally persistent cell migration via a more complex mechanism in which α4-integrin phosphorylation and paxillin binding act via both cooperative and independent pathways. We show that, in response to shear flow, α4β1-integrin binding to the CS-1 region of fibronectin was necessary and sufficient to promote directionally persistent cell migration when this integrin was ectopically expressed in CHO cells. Under shear flow, the α4β1-integrin-expressing cells formed a fan shape with broad lamellipodia at the front and retracted trailing edges at the back. This “fanning” activity was enhanced by disrupting paxillin binding alone and inhibited by disrupting phosphorylation alone or together with disrupting paxillin binding. Notably, the phosphorylation-disrupting mutation and the double mutation resulted in the formation of long trailing tails, suggesting that α4-integrin phosphorylation is required for trailing edge retraction/detachment independent of paxillin binding. Furthermore, the stable polarity and directional persistence of shear flow-stimulated cells were perturbed by the double mutation but not the single mutations alone, indicating that paxillin binding and α4-integrin phosphorylation can facilitate directionally persistent cell migration in an independent and compensatory manner. These findings provide a new insight into the mechanism by which integrins regulate directionally persistent cell migration.

Persistent cell migration emerges from a coupling between protrusion dynamics and polarized trafficking

2021 ◽  
Author(s):  
Kotryna Vaidžiulytė ◽  
Anne-Sophie Macé ◽  
Aude Battistella ◽  
William Beng ◽  
Kristine Schauer ◽  
...  
Keyword(s):  
Cell Migration ◽  
Live Cell Imaging ◽  
Cell Movement ◽  
Intrinsic Activity ◽  
Internal Cell ◽  
Polarized Trafficking ◽  
Cell Organization ◽  
Quantitative Properties ◽  
Long Timescales ◽  
Persistent Cell

AbstractMigrating cells present a variety of paths, from random to highly directional ones. While random movement can be explained by basal intrinsic activity, persistent movement requires stable polarization. Here, we quantitatively address emergence of persistent migration in RPE1 cells over long timescales. By live-cell imaging and dynamic micropatterning, we demonstrate that the Nucleus-Golgi axis aligns with direction of migration leading to efficient cell movement. We show that polarized trafficking is directed towards protrusions with a 20 min delay, and that migration becomes random after disrupting internal cell organization. Eventually, we prove that localized optogenetic Cdc42 activation orients the Nucleus-Golgi axis. Our work suggests that polarized trafficking stabilizes the protrusive activity of the cell, while protrusive activity orients this polarity axis, leading to persistent cell migration. Using a minimal physical model, we show that this feedback is sufficient to recapitulate the quantitative properties of cell migration in the timescale of hours.

scholarly journals MAP kinases and cell migration

2004 ◽  
Vol 117 (20) ◽  
pp. 4619-4628 ◽  
Author(s):  
C. Huang
Keyword(s):  
Cell Migration ◽  
Map Kinases

scholarly journals Regulation of Cell Contraction and Membrane Ruffling by Distinct Signals in Migratory Cells

1999 ◽  
Vol 146 (5) ◽  
pp. 1107-1116 ◽  
Author(s):  
David A. Cheresh ◽  
Jie Leng ◽  
Richard L. Klemke
Keyword(s):  
Cell Migration ◽  
Signaling Pathways ◽  
Map Kinases ◽  
Collagen Matrix ◽  
Adaptor Proteins ◽  
Cell Interaction ◽  
Cell Contraction ◽  
Rac Gtpase ◽  
Membrane Ruffling ◽  
Myosin Motors

Cell migration and wound contraction requires assembly of actin into a functional myosin motor unit capable of generating force. However, cell migration also involves formation of actin-containing membrane ruffles. Evidence is provided that actin-myosin assembly and membrane ruffling are regulated by distinct signaling pathways in the migratory cell. Interaction of cells with extracellular matrix proteins or cytokines promote cell migration through activation of the MAP kinases ERK1 and ERK2 as well as the molecular coupling of the adaptor proteins p130CAS and c-CrkII. ERK signaling is independent of CAS/Crk coupling and regulates myosin light chain phosphorylation leading to actin-myosin assembly during cell migration and cell-mediated contraction of a collagen matrix. In contrast, membrane ruffling, but not cell contraction, requires Rac GTPase activity and the formation of a CAS/Crk complex that functions in the context of the Rac activating protein DOCK180. Thus, during cell migration ERK and CAS/Crk coupling operate as components of distinct signaling pathways that control actin assembly into myosin motors and membrane ruffles, respectively.

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