scholarly journals Par-3-mediated Junctional Localization of the Lipid Phosphatase PTEN Is Required for Cell Polarity Establishment

2008 ◽  
Vol 283 (34) ◽  
pp. 23440-23449 ◽  
Author(s):  
Wei Feng ◽  
Hao Wu ◽  
Ling-Nga Chan ◽  
Mingjie Zhang
2003 ◽  
Vol 14 (12) ◽  
pp. 4958-4970 ◽  
Author(s):  
Keith G. Kozminski ◽  
Laure Beven ◽  
Elizabeth Angerman ◽  
Amy Hin Yan Tong ◽  
Charles Boone ◽  
...  

Polarized cell growth requires the coupling of a defined spatial site on the cell cortex to the apparatus that directs the establishment of cell polarity. In the budding yeast Saccharomyces cerevisiae, the Ras-family GTPase Rsr1p/Bud1p and its regulators select the proper site for bud emergence on the cell cortex. The Rho-family GTPase Cdc42p and its associated proteins then establish an axis of polarized growth by triggering an asymmetric organization of the actin cytoskeleton and secretory apparatus at the selected bud site. We explored whether a direct linkage exists between the Rsr1p/Bud1p and Cdc42p GTPases. Here we show specific genetic interactions between RSR1/BUD1 and particular cdc42 mutants defective in polarity establishment. We also show that Cdc42p coimmunoprecipitated with Rsr1p/Bud1p from yeast extracts. In vitro studies indicated a direct interaction between Rsr1p/Bud1p and Cdc42p, which was enhanced by Cdc24p, a guanine nucleotide exchange factor for Cdc42p. Our findings suggest that Cdc42p interacts directly with Rsr1p/Bud1p in vivo, providing a novel mechanism by which direct contact between a Ras-family GTPase and a Rho-family GTPase links the selection of a growth site to polarity establishment.


2013 ◽  
Vol 24 (7) ◽  
pp. 945-963 ◽  
Author(s):  
Wangsun Choi ◽  
Nathan J. Harris ◽  
Kaelyn D. Sumigray ◽  
Mark Peifer

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.


2018 ◽  
pp. 51-71
Author(s):  
Arthur J. Molendijk ◽  
Olaf Tietz ◽  
Benedetto Ruperti ◽  
Ivan A. Paponov ◽  
Klaus Palme

2019 ◽  
Author(s):  
Xue Pan ◽  
Linjing Fang ◽  
Jianfeng Liu ◽  
Betul Senay-Aras ◽  
Wenwei Lin ◽  
...  

AbstractCell polarity is fundamental to the development of both eukaryotic and prokaryotic organisms, yet the mechanism of its establishment remains poorly understood. Here we show that signal-activated nanoclustering of membrane proteins and a cytoskeleton-based feedback loop provide an important mechanism for the establishment of cell polarity. The phytohormone auxin promoted sterol-dependent nanoclustering of cell surface transmembrane receptor-like kinase 1 (TMK1) to initiate cell polarity during the morphogenesis of Arabidopsis puzzle piece-shaped leaf pavement cells (PC). Auxin-triggered nanoclustering of TMK1 stabilized flotillin-associated ordered nanodomains, which were essential for auxin-mediated formation of ROP6 GTPase nanoclusters that act downstream TMK1 to promote cortical microtubule ordering. Mathematical modeling further demonstrated the essential role of this auxin-mediated stabilization of TMK1 and ROP6 nanoclusters, and predicted the additional requirement of ROP6-dependent cortical microtubules for further stabilization of TMK1-sterol nanodomains and the polarization of PC. This prediction was experimentally validated by genetic and biochemical data. Our studies reveal a new paradigm for polarity establishment: A diffusive signal triggers cell polarization by activating cell surface receptor-mediated lateral segregation of signaling components and a cytoskeleton-mediated positive feedback loop of nanodomain stabilization.HighlightsSterols are required for cell polarity in Arabidopsis leaf epidermal cellsAuxin promotes lipid ordering and polar distribution of ordered lipid nanodomains at the plasma membrane (PM)Auxin stabilizes sterol-dependent nanoclustering of transmembrane kinase (TMK1), a PM auxin signal transducerAuxin-induced TMK1 nanoclustering is required but insufficient for cell polarizationMicrotubule-based feedback stabilization of the auxin-induced TMK1 nanodomains can generate cell polarity


PLoS Genetics ◽  
2018 ◽  
Vol 14 (5) ◽  
pp. e1007391 ◽  
Author(s):  
Giovanna M. Collu ◽  
Andreas Jenny ◽  
Konstantin Gaengel ◽  
Ivana Mirkovic ◽  
Mei-ling Chin ◽  
...  

2018 ◽  
Vol 15 (3) ◽  
pp. 293-300 ◽  
Author(s):  
Peter Gross ◽  
K. Vijay Kumar ◽  
Nathan W. Goehring ◽  
Justin S. Bois ◽  
Carsten Hoege ◽  
...  

2019 ◽  
Vol 160 ◽  
pp. 103583
Author(s):  
Pedro M. Domingos ◽  
Andreas Jenny ◽  
Keon F. Combie ◽  
David del Alamo ◽  
Marek Mlodzik ◽  
...  

2003 ◽  
Vol 14 (2) ◽  
pp. 670-684 ◽  
Author(s):  
Juana Magdalena ◽  
Thomas H. Millard ◽  
Sandrine Etienne-Manneville ◽  
Sophie Launay ◽  
Helen K. Warwick ◽  
...  

Cell motility and cell polarity are essential for morphogenesis, immune system function, and tissue repair. Many animal cells move by crawling, and one main driving force for movement is derived from the coordinated assembly and disassembly of actin filaments. As tissue culture cells migrate to close a scratch wound, this directional extension is accompanied by Golgi apparatus reorientation, to face the leading wound edge, giving the motile cell inherent polarity aligned relative to the wound edge and to the direction of cell migration. Cellular proteins essential for actin polymerization downstream of Rho family GTPases include the Arp2/3 complex as an actin nucleator and members of the Wiskott–Aldrich Syndrome protein (WASP) family as activators of the Arp2/3 complex. We therefore analyzed the involvement of the Arp2/3 complex and WASP-family proteins in in vitro wound healing assays using NIH 3T3 fibroblasts and astrocytes. In NIH 3T3 cells, we found that actin and Arp2/3 complex contributed to cell polarity establishment. Moreover, overexpression of N-terminal fragments of Scar2 (but not N-WASP or Scar1 or Scar3) interfere with NIH 3T3 Golgi polarization but not with cell migration. In contrast, actin, Arp2/3, and WASP-family proteins did not appear to be involved in Golgi polarization in astrocytes. Our results thus indicate that the requirement for Golgi polarity establishment is cell-type specific. Furthermore, in NIH 3T3 cells, Scar2 and the Arp2/3 complex appear to be involved in the establishment and maintenance of Golgi polarity during directed migration.


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