scholarly journals Migrating fibroblasts reorient directionality by a metastable, PI3K-dependent mechanism

2012 ◽  
Vol 197 (1) ◽  
pp. 105-114 ◽  
Author(s):  
Erik S. Welf ◽  
Shoeb Ahmed ◽  
Heath E. Johnson ◽  
Adam T. Melvin ◽  
Jason M. Haugh
Keyword(s):  
Cell Migration ◽  
Total Internal Reflection ◽  
Mesenchymal Cell ◽  
Lateral Spreading ◽  
Pi3k Signaling ◽  
Spatial Cues ◽  
Cell Protrusion ◽  
Pi3k Inhibition ◽  
Phosphoinositide 3 Kinase ◽  
Dependent Mechanism

Mesenchymal cell migration as exhibited by fibroblasts is distinct from amoeboid cell migration and is characterized by dynamic competition among multiple protrusions, which determines directional persistence and responses to spatial cues. Localization of phosphoinositide 3-kinase (PI3K) signaling is thought to play a broadly important role in cell motility, yet the context-dependent functions of this pathway have not been adequately elucidated. By mapping the spatiotemporal dynamics of cell protrusion/retraction and PI3K signaling monitored by total internal reflection fluorescence microscopy, we show that randomly migrating fibroblasts reorient polarity through PI3K-dependent branching and pivoting of protrusions. PI3K inhibition did not affect the initiation of newly branched protrusions, nor did it prevent protrusion induced by photoactivation of Rac. Rather, PI3K signaling increased after, not before, the onset of local protrusion and was required for the lateral spreading and stabilization of nascent branches. During chemotaxis, the branch experiencing the higher chemoattractant concentration was favored, and, thus, the cell reoriented so as to align with the external gradient.

scholarly journals F-actin bundles direct the initiation and orientation of lamellipodia through adhesion-based signaling

2015 ◽  
Vol 208 (4) ◽  
pp. 443-455 ◽  
Author(s):  
Heath E. Johnson ◽  
Samantha J. King ◽  
Sreeja B. Asokan ◽  
Jeremy D. Rotty ◽  
James E. Bear ◽  
...  
Keyword(s):  
Focal Adhesion ◽  
Total Internal Reflection ◽  
Cell Shape ◽  
Platelet Derived Growth Factor ◽  
Pi3k Signaling ◽  
Actin Bundles ◽  
Signaling Dynamics ◽  
Ratiometric Imaging ◽  
Phosphoinositide 3 Kinase

Mesenchymal cells such as fibroblasts are weakly polarized and reorient directionality by a lamellipodial branching mechanism that is stabilized by phosphoinositide 3-kinase (PI3K) signaling. However, the mechanisms by which new lamellipodia are initiated and directed are unknown. Using total internal reflection fluorescence microscopy to monitor cytoskeletal and signaling dynamics in migrating cells, we show that peripheral F-actin bundles/filopodia containing fascin-1 serve as templates for formation and orientation of lamellipodia. Accordingly, modulation of fascin-1 expression tunes cell shape, quantified as the number of morphological extensions. Ratiometric imaging reveals that F-actin bundles/filopodia play both structural and signaling roles, as they prime the activation of PI3K signaling mediated by integrins and focal adhesion kinase. Depletion of fascin-1 ablated fibroblast haptotaxis on fibronectin but not platelet-derived growth factor chemotaxis. Based on these findings, we conceptualize haptotactic sensing as an exploration, with F-actin bundles directing and lamellipodia propagating the process and with signaling mediated by adhesions playing the role of integrator.

The class II phosphoinositide 3-kinase PI3K-C2β regulates cell migration by a PtdIns(3)P dependent mechanism

2005 ◽  
Vol 205 (3) ◽  
pp. 452-462 ◽  
Author(s):  
Jan Domin ◽  
Lisa Harper ◽  
Deborah Aubyn ◽  
Matthew Wheeler ◽  
Oliver Florey ◽  
...  
Keyword(s):  
Cell Migration ◽  
Class Ii ◽  
Phosphoinositide 3 Kinase ◽  
Dependent Mechanism

scholarly journals Reciprocal regulation among TRPV1 channels and phosphoi nos itide 3-kinase in response to nerve growth factor

2018 ◽  
Author(s):  
Anastasiia Stratiievska ◽  
Sara Nelson ◽  
Eric N. Senning ◽  
Jonathan D. Lautz ◽  
Stephen E.P. Smith ◽  
...  
Keyword(s):  
Total Internal Reflection ◽  
Inflammatory Mediator ◽  
Trp Channels ◽  
Pi3k Signaling ◽  
Reciprocal Regulation ◽  
Trpv1 Channels ◽  
Pi3k Activity ◽  
Trpv Channels ◽  
Receptor Neurons ◽  
Phosphoinositide 3 Kinase

AbstractAlthough it has been known for over a decade that the inflammatory mediator NGF sensitizes pain-receptor neurons through increased trafficking of TRPV1 channels to the plasma membrane, the mechanism by which this occurs remains mysterious. NGF activates phosphoinositide 3-kinase (PI3K), the enzyme that generates PIP3, and PI3K activity is required for sensitization. One tantalizing hint came from the finding that the N-terminal region of TRPV1 interacts directly with PI3K. Using 2-color total internal reflection fluorescence microscopy, we show that TRPV1 potentiates NGF-induced PI3K activity. A soluble TRPV1 fragment corresponding to the N-terminal Ankyrin repeats domain (ARD) was sufficient to produce this potentiation, indicating that allosteric regulation was involved. Further, other TRPV channels with conserved ARDs also potentiated NGF-induced PI3K activity whereas TRP channels lacking ARDs did not. Our data demonstrate a novel reciprocal regulation of PI3K signaling by the ARD of TRPV channels.

scholarly journals Reciprocal regulation among TRPV1 channels and phosphoinositide 3-kinase in response to nerve growth factor

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Anastasiia Stratiievska ◽  
Sara Nelson ◽  
Eric N Senning ◽  
Jonathan D Lautz ◽  
Stephen EP Smith ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Total Internal Reflection ◽  
Inflammatory Mediator ◽  
Pi3k Signaling ◽  
Reciprocal Regulation ◽  
Trpv1 Channels ◽  
Pi3k Activity ◽  
Trpv Channels ◽  
Receptor Neurons ◽  
Phosphoinositide 3 Kinase

Although it has been known for over a decade that the inflammatory mediator NGF sensitizes pain-receptor neurons through increased trafficking of TRPV1 channels to the plasma membrane, the mechanism by which this occurs remains mysterious. NGF activates phosphoinositide 3-kinase (PI3K), the enzyme that generates PI(3,4)P2 and PIP3, and PI3K activity is required for sensitization. One tantalizing hint came from the finding that the N-terminal region of TRPV1 interacts directly with PI3K. Using two-color total internal reflection fluorescence microscopy, we show that TRPV1 potentiates NGF-induced PI3K activity. A soluble TRPV1 fragment corresponding to the N-terminal Ankyrin repeats domain (ARD) was sufficient to produce this potentiation, indicating that allosteric regulation was involved. Further, other TRPV channels with conserved ARDs also potentiated NGF-induced PI3K activity. Our data demonstrate a novel reciprocal regulation of PI3K signaling by the ARD of TRPV channels.

scholarly journals Light-activated Frizzled7 reveals a permissive role of non-canonical wnt signaling in mesendoderm cell migration

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Daniel Čapek ◽  
Michael Smutny ◽  
Alexandra-Madelaine Tichy ◽  
Maurizio Morri ◽  
Harald Janovjak ◽  
...  
Keyword(s):  
Cell Migration ◽  
Wnt Signaling ◽  
Mesenchymal Cell ◽  
Cell Polarization ◽  
Canonical Wnt Signaling ◽  
Cell Protrusion ◽  
Directed Cell Migration ◽  
Ectopic Activation ◽  
And Migration ◽  
Canonical Wnt

Non-canonical Wnt signaling plays a central role for coordinated cell polarization and directed migration in metazoan development. While spatiotemporally restricted activation of non-canonical Wnt-signaling drives cell polarization in epithelial tissues, it remains unclear whether such instructive activity is also critical for directed mesenchymal cell migration. Here, we developed a light-activated version of the non-canonical Wnt receptor Frizzled 7 (Fz7) to analyze how restricted activation of non-canonical Wnt signaling affects directed anterior axial mesendoderm (prechordal plate, ppl) cell migration within the zebrafish gastrula. We found that Fz7 signaling is required for ppl cell protrusion formation and migration and that spatiotemporally restricted ectopic activation is capable of redirecting their migration. Finally, we show that uniform activation of Fz7 signaling in ppl cells fully rescues defective directed cell migration in fz7 mutant embryos. Together, our findings reveal that in contrast to the situation in epithelial cells, non-canonical Wnt signaling functions permissively rather than instructively in directed mesenchymal cell migration during gastrulation.

Mechanics and Mechanisms of 3D Mesenchymal Cell Migration

2020 ◽  
Author(s):  
Andrew D. Doyle ◽  
Daniel J. Sykora ◽  
Gustavo G. Pacheco ◽  
Matthew L. Kutys ◽  
Kenneth M. Yamada
Keyword(s):  
Cell Migration ◽  
Mesenchymal Cell

scholarly journals Glycolysis fuels phosphoinositide 3-kinase signaling to bolster T cell immunity

Science ◽  
2021 ◽  
Vol 371 (6527) ◽  
pp. 405-410
Author(s):  
Ke Xu ◽  
Na Yin ◽  
Min Peng ◽  
Efstathios G. Stamatiades ◽  
Amy Shyu ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Glycolytic Enzyme ◽  
T Cell Immunity ◽  
Pi3k Signaling ◽  
Growth Factor Signaling ◽  
Atp Production ◽  
T Effector Cells ◽  
Cell Immunity ◽  
Phosphoinositide 3 Kinase

Infection triggers expansion and effector differentiation of T cells specific for microbial antigens in association with metabolic reprograming. We found that the glycolytic enzyme lactate dehydrogenase A (LDHA) is induced in CD8+ T effector cells through phosphoinositide 3-kinase (PI3K) signaling. In turn, ablation of LDHA inhibits PI3K-dependent phosphorylation of Akt and its transcription factor target Foxo1, causing defective antimicrobial immunity. LDHA deficiency cripples cellular redox control and diminishes adenosine triphosphate (ATP) production in effector T cells, resulting in attenuated PI3K signaling. Thus, nutrient metabolism and growth factor signaling are highly integrated processes, with glycolytic ATP serving as a rheostat to gauge PI3K-Akt-Foxo1 signaling in the control of T cell immunity. Such a bioenergetic mechanism for the regulation of signaling may explain the Warburg effect.

The P2Y12receptor induces platelet aggregation through weak activation of the αIIbβ3integrin - a phosphoinositide 3-kinase-dependent mechanism

FEBS Letters ◽  
2001 ◽  
Vol 505 (2) ◽  
pp. 281-290 ◽  
Author(s):  
G. Kauffenstein ◽  
W. Bergmeier ◽  
A. Eckly ◽  
P. Ohlmann ◽  
C. Léon ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Phosphoinositide 3 Kinase ◽  
Dependent Mechanism
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