Cell polarization mechanisms during directed cell migration

2005 ◽  
Vol 7 (4) ◽  
pp. 336-337 ◽  
Author(s):  
Anna Huttenlocher
Keyword(s):  
Cell Migration ◽  
Cell Polarization ◽  
Directed Cell Migration

scholarly journals Paxillin-Kinase-Linker Tyrosine Phosphorylation Regulates Directional Cell Migration

2009 ◽  
Vol 20 (22) ◽  
pp. 4706-4719 ◽  
Author(s):  
Jianxin A. Yu ◽  
Nicholas O. Deakin ◽  
Christopher E. Turner
Keyword(s):  
Cell Migration ◽  
Cell Adhesion ◽  
Growth Factor ◽  
Tyrosine Phosphorylation ◽  
Wound Repair ◽  
Cell Polarization ◽  
Dependent Manner ◽  
Directed Cell Migration ◽  
Focal Adhesion Protein ◽  
Directional Cell Migration

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.

scholarly journals Cdc42 localization and cell polarity depend on membrane traffic

2010 ◽  
Vol 191 (7) ◽  
pp. 1261-1269 ◽  
Author(s):  
Naël Osmani ◽  
Florent Peglion ◽  
Philippe Chavrier ◽  
Sandrine Etienne-Manneville
Keyword(s):  
Cell Migration ◽  
Cell Polarity ◽  
Membrane Trafficking ◽  
Membrane Traffic ◽  
Leading Edge ◽  
Cell Polarization ◽  
Membrane Dynamics ◽  
Cell Functions ◽  
Directed Cell Migration ◽  
Division Cell

Cell polarity is essential for cell division, cell differentiation, and most differentiated cell functions including cell migration. The small G protein Cdc42 controls cell polarity in a wide variety of cellular contexts. Although restricted localization of active Cdc42 seems to be important for its distinct functions, mechanisms responsible for the concentration of active Cdc42 at precise cortical sites are not fully understood. In this study, we show that during directed cell migration, Cdc42 accumulation at the cell leading edge relies on membrane traffic. Cdc42 and its exchange factor βPIX localize to intracytosplasmic vesicles. Inhibition of Arf6-dependent membrane trafficking alters the dynamics of Cdc42-positive vesicles and abolishes the polarized recruitment of Cdc42 and βPIX to the leading edge. Furthermore, we show that Arf6-dependent membrane dynamics is also required for polarized recruitment of Rac and the Par6–aPKC polarity complex and for cell polarization. Our results demonstrate influence of membrane dynamics on the localization and activation of Cdc42 and consequently on directed cell migration.

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.

scholarly journals Vimentin Regulates Scribble Activity by Protecting It from Proteasomal Degradation

2009 ◽  
Vol 20 (12) ◽  
pp. 2841-2855 ◽  
Author(s):  
Dominic C.Y. Phua ◽  
Patrick O. Humbert ◽  
Walter Hunziker
Keyword(s):  
Cell Migration ◽  
Mdck Cells ◽  
Umbilical Vein ◽  
Cell Aggregation ◽  
Proteasomal Degradation ◽  
Cell Polarization ◽  
Vimentin Expression ◽  
Directed Cell Migration ◽  
Directional Movement ◽  
Umbilical Vein Endothelial Cells

Scribble (Scrib), Discs large, and Lethal giant larvae form a protein complex that regulates different aspects of cell polarization, including apical–basal asymmetry in epithelial cells and anterior–posterior polarity in migrating cells. Here, we show that Scrib interacts with the intermediate filament cytoskeleton in epithelial Madin-Darby canine kidney (MDCK) cells and endothelial human umbilical vein endothelial cells. Scrib binds vimentin via its postsynaptic density 95/disc-large/zona occludens domains and in MDCK cells redistributes from filaments to the plasma membrane during the establishment of cell–cell contacts. RNA interference-mediated silencing of Scrib, vimentin, or both in MDCK cells results in defects in the polarization of the Golgi apparatus during cell migration. Concomitantly, wound healing is delayed due to the loss of directional movement. Furthermore, cell aggregation is dependent on both Scrib and vimentin. The similar phenotypes observed after silencing either Scrib or vimentin support a coordinated role for the two proteins in cell migration and aggregation. Interestingly, silencing of vimentin leads to an increased proteasomal degradation of Scrib. Thus, the upregulation of vimentin expression during epithelial to mesenchymal transitions may stabilize Scrib to promote directed cell migration.

scholarly journals Centrosome guides spatial activation of Rac to control cell polarization and directed cell migration

2019 ◽  
Vol 2 (1) ◽  
pp. e201800135 ◽  
Author(s):  
Hung-Wei Cheng ◽  
Cheng-Te Hsiao ◽  
Yin-Quan Chen ◽  
Chi-Ming Huang ◽  
Seng-I Chan ◽  
...  
Keyword(s):  
Cell Migration ◽  
Control Cell ◽  
Focal Adhesions ◽  
Cell Polarization ◽  
Functional Domain ◽  
Cell Periphery ◽  
Nucleotide Exchange ◽  
Directed Cell Migration ◽  
Nucleotide Exchange Factor ◽  
Cell Front

Directed cell migration requires centrosome-mediated cell polarization and dynamical control of focal adhesions (FAs). To examine how FAs cooperate with centrosomes for directed cell migration, we used centrosome-deficient cells and found that loss of centrosomes enhanced the formation of acentrosomal microtubules, which failed to form polarized structures in wound-edge cells. In acentrosomal cells, we detected higher levels of Rac1-guanine nucleotide exchange factor TRIO (Triple Functional Domain Protein) on microtubules and FAs. Acentrosomal microtubules deliver TRIO to FAs for Rac1 regulation. Indeed, centrosome disruption induced excessive Rac1 activation around the cell periphery via TRIO, causing rapid FA turnover, a disorganized actin meshwork, randomly protruding lamellipodia, and loss of cell polarity. This study reveals the importance of centrosomes to balance the assembly of centrosomal and acentrosomal microtubules and to deliver microtubule-associated TRIO proteins to FAs at the cell front for proper spatial activation of Rac1, FA turnover, lamillipodial protrusion, and cell polarization, thereby allowing directed cell migration.

scholarly journals The Rac-GAP Bcr is a novel regulator of the Par complex that controls cell polarity

2013 ◽  
Vol 24 (24) ◽  
pp. 3857-3868 ◽  
Author(s):  
Anjana S. Narayanan ◽  
Steve B. Reyes ◽  
Kyongmi Um ◽  
Joseph H. McCarty ◽  
Kimberley F. Tolias
Keyword(s):  
Cell Migration ◽  
Cell Polarity ◽  
Leading Edge ◽  
Cell Polarization ◽  
Nucleotide Exchange ◽  
Complex Activity ◽  
Guanine Nucleotide Exchange ◽  
Directed Cell Migration ◽  
Nucleotide Exchange Factor ◽  
T Lymphoma

Cell polarization is essential for many biological processes, including directed cell migration, and loss of polarity contributes to pathological conditions such as cancer. The Par complex (Par3, Par6, and PKCζ) controls cell polarity in part by recruiting the Rac-specific guanine nucleotide exchange factor T-lymphoma invasion and metastasis 1 (Tiam1) to specialized cellular sites, where Tiam1 promotes local Rac1 activation and cytoskeletal remodeling. However, the mechanisms that restrict Par-Tiam1 complex activity to the leading edge to maintain cell polarity during migration remain unclear. We identify the Rac-specific GTPase-activating protein (GAP) breakpoint cluster region protein (Bcr) as a novel regulator of the Par-Tiam1 complex. We show that Bcr interacts with members of the Par complex and inhibits both Rac1 and PKCζ signaling. Loss of Bcr results in faster, more random migration and striking polarity defects in astrocytes. These polarity defects are rescued by reducing PKCζ activity or by expressing full-length Bcr, but not an N-terminal deletion mutant or the homologous Rac-GAP, Abr, both of which fail to associate with the Par complex. These results demonstrate that Bcr is an integral member of the Par-Tiam1 complex that controls polarized cell migration by locally restricting both Rac1 and PKCζ function.

scholarly journals Excitable Networks in Directed Cell Migration

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