scholarly journals Cdc42 Is Not Essential for Filopodium Formation, Directed Migration, Cell Polarization, and Mitosis in Fibroblastoid Cells

2005 ◽  
Vol 16 (10) ◽  
pp. 4473-4484 ◽  
Author(s):  
Aleksandra Czuchra ◽  
Xunwei Wu ◽  
Hannelore Meyer ◽  
Jolanda van Hengel ◽  
Timm Schroeder ◽  
...  
Keyword(s):  
Cell Polarity ◽  
Cell Shape ◽  
Cell Polarization ◽  
Small Gtpase ◽  
Dominant Negative ◽  
Directed Migration ◽  
Membrane Blebbing ◽  
Directed Cell Migration ◽  
Rho Family ◽  
Filopodium Formation

Cdc42 is a small GTPase involved in the regulation of the cytoskeleton and cell polarity. To test whether Cdc42 has an essential role in the formation of filopodia or directed cell migration, we generated Cdc42-deficient fibroblastoid cells by conditional gene inactivation. We report here that loss of Cdc42 did not affect filopodium or lamellipodium formation and had no significant influence on the speed of directed migration nor on mitosis. Cdc42-deficient cells displayed a more elongated cell shape and had a reduced area. Furthermore, directionality during migration and reorientation of the Golgi apparatus into the direction of migration was decreased. However, expression of dominant negative Cdc42 in Cdc42-null cells resulted in strongly reduced directed migration, severely reduced single cell directionality, and complete loss of Golgi polarization and of directionality of protrusion formation toward the wound, as well as membrane blebbing. Thus, our data show that besides Cdc42 additional GTPases of the Rho-family, which share GEFs with Cdc42, are involved in the establishment and maintenance of cell polarity during directed migration.

scholarly journals The CDC42 Homolog of the Dimorphic FungusPenicillium marneffei Is Required for Correct Cell Polarization during Growth but Not Development

2001 ◽  
Vol 183 (11) ◽  
pp. 3447-3457 ◽  
Author(s):  
Kylie J. Boyce ◽  
Michael J. Hynes ◽  
Alex Andrianopoulos
Keyword(s):  
Cell Shape ◽  
Pathogenic Fungus ◽  
Cell Polarization ◽  
Dominant Negative ◽  
Yeast Cells ◽  
Polarized Growth ◽  
Temperature Dependent ◽  
Human Pathogenic Fungus ◽  
Rho Family

ABSTRACT The opportunistic human pathogenic fungus Penicillium marneffei is dimorphic and is thereby capable of growth either as filamentous multinucleate hyphae or as uninucleate yeast cells which divide by fission. The dimorphic switch is temperature dependent and requires regulated changes in morphology and cell shape. Cdc42p is a Rho family GTPase which in Saccharomyces cerevisiae is required for changes in polarized growth during mating and pseudohyphal development. Cdc42p homologs in higher organisms are also associated with changes in cell shape and polarity. We have cloned a highly conserved CDC42 homolog from P. marneffeinamed cflA. By the generation of dominant-negative and dominant-activated cflA transformants, we have shown that CflA initiates polarized growth and extension of the germ tube and subsequently maintains polarized growth in the vegetative mycelium. CflA is also required for polarization and determination of correct cell shape during yeast-like growth, and active CflA is required for the separation of yeast cells. However, correct cflAfunction is not required for dimorphic switching and does not appear to play a role during the generation of specialized structures during asexual development. In contrast, heterologous expression ofcflA alleles in Aspergillus nidulansprevented conidiation.

scholarly journals Integrin-linked Kinase Interactions with ELMO2 Modulate Cell Polarity

2009 ◽  
Vol 20 (13) ◽  
pp. 3033-3043 ◽  
Author(s):  
Ernest Ho ◽  
Tames Irvine ◽  
Gregory J.A. Vilk ◽  
Gilles Lajoie ◽  
Kodi S. Ravichandran ◽  
...  
Keyword(s):  
Cell Motility ◽  
Cell Polarity ◽  
Tissue Regeneration ◽  
Protein Complex ◽  
Cell Polarization ◽  
Dominant Negative ◽  
Forward Movement ◽  
Directed Migration ◽  
Polarized Cells ◽  
Integrin Linked Kinase

Cell polarization is a key prerequisite for directed migration during development, tissue regeneration, and metastasis. Integrin-linked kinase (ILK) is a scaffold protein essential for cell polarization, but very little is known about the precise mechanisms whereby ILK modulates polarization in normal epithelia. Elucidating these mechanisms is essential to understand tissue morphogenesis, transformation, and repair. Here we identify a novel ILK protein complex that includes Engulfment and Cell Motility 2 (ELMO2). We also demonstrate the presence of RhoG in ILK–ELMO2 complexes, and the localization of this multiprotein species specifically to the leading lamellipodia of polarized cells. Significantly, the ability of RhoG to bind ELMO is crucial for ILK induction of cell polarization, and the joint expression of ILK and ELMO2 synergistically promotes the induction of front-rear polarity and haptotactic migration. This places RhoG–ELMO2–ILK complexes in a key position for the development of cell polarity and forward movement. Although ILK is a component of many diverse multiprotein species that may contribute to cell polarization, expression of dominant-negative ELMO2 mutants is sufficient to abolish the ability of ILK to promote cell polarization. Thus, its interaction with ELMO2 and RhoG is essential for the ability of ILK to induce front-rear cell polarity.

Cell polarity and tissue patterning in plants

Development ◽  
1991 ◽  
Vol 113 (Supplement_1) ◽  
pp. 83-93 ◽  
Author(s):  
Tsvi Sachs
Keyword(s):  
Cell Polarity ◽  
Cell Shape ◽  
Auxin Transport ◽  
Developmental Stages ◽  
Important Determinant ◽  
Genetic System ◽  
Cell Patterning ◽  
Cell Polarization ◽  
Sources And Sinks ◽  
Tissue Patterning

Cell polarization is the specialization of developmental events along one orientation or one direction. Such polarization must be an early, essential stage of tissue patterning. The specification of orientation could not occur only at the level of the genetic system and it must express a coordination of events in many cells. There is a positive feedback relation between cell polarization and the transport of the known hormone auxin: polarity determines oriented auxin transport while transport itself induces both new and continued polarization. Since cell polarization increases gradually, this feedback leads to the canalization of transport – and of the associated cell differentiation – along defined strands of specialized cells. Recent work has shown that the same canalized flow can also be an important determinant of cell shape. In primordial, embryonic regions cell growth is oriented along the flow of auxin from the shoot towards the root. In later developmental stages the cells respond to the same flow by growing in girth, presumably adjusting the capacity of the tissues to the flow of signals. Finally, disrupted flow near wounds results in the development of relatively unorganized callus. Continued callus development appears to require the participation of the cells, as sources and sinks of auxin and other signals. The overall picture to emerge suggests that cell patterning can result from competition between cells acting as preferred channels, sources and sinks for developmental signals.

scholarly journals Rap1 and Canoe/afadin are essential for establishment of apical–basal polarity in the Drosophila embryo

2013 ◽  
Vol 24 (7) ◽  
pp. 945-963 ◽  
Author(s):  
Wangsun Choi ◽  
Nathan J. Harris ◽  
Kaelyn D. Sumigray ◽  
Mark Peifer
Keyword(s):  
Protein Kinase C ◽  
Cell Polarity ◽  
Cell Shape ◽  
Adherens Junctions ◽  
Small Gtpase ◽  
Drosophila Embryo ◽  
Current View ◽  
Kinase C ◽  
Polarity Establishment ◽  
Drosophila Embryos

The establishment and maintenance of apical–basal cell polarity is critical for assembling epithelia and maintaining organ architecture. Drosophila embryos provide a superb model. In the current view, apically positioned Bazooka/Par3 is the initial polarity cue as cells form during cellularization. Bazooka then helps to position both adherens junctions and atypical protein kinase C (aPKC). Although a polarized cytoskeleton is critical for Bazooka positioning, proteins mediating this remained unknown. We found that the small GTPase Rap1 and the actin-junctional linker Canoe/afadin are essential for polarity establishment, as both adherens junctions and Bazooka are mispositioned in their absence. Rap1 and Canoe do not simply organize the cytoskeleton, as actin and microtubules become properly polarized in their absence. Canoe can recruit Bazooka when ectopically expressed, but they do not obligatorily colocalize. Rap1 and Canoe play continuing roles in Bazooka localization during gastrulation, but other polarity cues partially restore apical Bazooka in the absence of Rap1 or Canoe. We next tested the current linear model for polarity establishment. Both Bazooka and aPKC regulate Canoe localization despite being “downstream” of Canoe. Further, Rap1, Bazooka, and aPKC, but not Canoe, regulate columnar cell shape. These data reshape our view, suggesting that polarity establishment is regulated by a protein network rather than a linear pathway.

scholarly journals Small GTPase RhoG Is a Key Regulator for Neurite Outgrowth in PC12 Cells

2000 ◽  
Vol 20 (19) ◽  
pp. 7378-7387 ◽  
Author(s):  
Hironori Katoh ◽  
Hidekazu Yasui ◽  
Yoshiaki Yamaguchi ◽  
Junko Aoki ◽  
Hirotada Fujita ◽  
...  
Keyword(s):  
Neurite Outgrowth ◽  
Pc12 Cells ◽  
Morphological Changes ◽  
Cell Types ◽  
Small Gtpases ◽  
Small Gtpase ◽  
Dominant Negative ◽  
Wild Type ◽  
Rho Family ◽  
Constitutively Active

ABSTRACT The Rho family of small GTPases has been implicated in cytoskeletal reorganization and subsequent morphological changes in various cell types. Among them, Rac and Cdc42 have been shown to be involved in neurite outgrowth in neuronal cells. In this study, we examined the role of RhoG, another member of Rho family GTPases, in nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells. Expression of wild-type RhoG in PC12 cells induced neurite outgrowth in the absence of NGF, and the morphology of wild-type RhoG-expressing cells was similar to that of NGF-differentiated cells. Constitutively active RhoG-transfected cells extended short neurites but developed large lamellipodial or filopodial structures at the tips of neurites. RhoG-induced neurite outgrowth was inhibited by coexpression with dominant-negative Rac1 or Cdc42. In addition, expression of constitutively active RhoG elevated endogenous Rac1 and Cdc42 activities. We also found that the NGF-induced neurite outgrowth was enhanced by expression of wild-type RhoG whereas expression of dominant-negative RhoG suppressed the neurite outgrowth. Furthermore, constitutively active Ras-induced neurite outgrowth was also suppressed by dominant-negative RhoG. Taken together, these results suggest that RhoG is a key regulator in NGF-induced neurite outgrowth, acting downstream of Ras and upstream of Rac1 and Cdc42 in PC12 cells.

scholarly journals Big roles for small GTPases in the control of directed cell movement

2006 ◽  
Vol 401 (2) ◽  
pp. 377-390 ◽  
Author(s):  
Pascale G. Charest ◽  
Richard A. Firtel
Keyword(s):  
Molecular Mechanisms ◽  
Cell Movement ◽  
Small Gtpases ◽  
Cell Polarization ◽  
Small Gtpase ◽  
Cellular Growth ◽  
Cellular Motility ◽  
Gradient Sensing ◽  
Directed Cell Migration ◽  
Shed Light

Small GTPases are involved in the control of diverse cellular behaviours, including cellular growth, differentiation and motility. In addition, recent studies have revealed new roles for small GTPases in the regulation of eukaryotic chemotaxis. Efficient chemotaxis results from co-ordinated chemoattractant gradient sensing, cell polarization and cellular motility, and accumulating data suggest that small GTPase signalling plays a central role in each of these processes as well as in signal relay. The present review summarizes these recent findings, which shed light on the molecular mechanisms by which small GTPases control directed 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.

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