期刊论文详细信息
BMC Cell Biology
Regulation of the microtubular cytoskeleton by Polycystin-1 favors focal adhesions turnover to modulate cell adhesion and migration
Alessandra Boletta4  Letizia Lanzetti3  Amanda Oldani2  Nadia Ducano3  Gianfranco Distefano4  Chiara De Pascalis1  Maddalena Castelli4 
[1]Current Address: International PhD Program, Institut Pasteur, Paris, France
[2]IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy
[3]Department of Oncology, University of Torino, Torino, Italy
[4]Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy
关键词: Focal adhesion kinase;    Focal adhesion turnover;    Adhesion;    Microtubules;    Migration;    Polycystin-1;   
Others  :  1211779
DOI  :  10.1186/s12860-015-0059-3
 received in 2015-02-04, accepted in 2015-04-22,  发布年份 2015
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【 摘 要 】

Background

Polycystin-1 (PC-1) is a large plasma membrane receptor, encoded by the PKD1 gene, which is mutated in most cases of Autosomal Dominant Polycystic Kidney Disease (ADPKD). The disease is characterized by renal cysts. The precise function of PC-1 remains elusive, although several studies suggest that it can regulate the cellular shape in response to external stimuli. We and others reported that PC-1 regulates the actin cytoskeleton and cell migration.

Results

Here we show that cells over-expressing PC-1 display enhanced adhesion rates to the substrate, while cells lacking PC-1 have a reduced capability to adhere. In search for the mechanism responsible for this new property of PC-1 we found that this receptor is able to regulate the stability of the microtubules, in addition to its capability to regulate the actin cytoskeleton. The two cytoskeletal components are acting in a coordinated fashion. Notably, we uncovered that PC-1 regulation of the microtubule cytoskeleton impacts on the turnover rates of focal adhesions in migrating cells and we link all these properties to the capability of PC-1 to regulate the activation state of Focal Adhesion Kinase (FAK).

Conclusions

In this study we show several new features of the PC-1 receptor in modulating microtubules and adhesion dynamics, which are essential for its capability to regulate migration.

【 授权许可】

   
2015 Castelli et al.; licensee BioMed Central.

【 预 览 】
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【 参考文献 】
  • [1]Boletta A, Germino GG. Role of polycystins in renal tubulogenesis. Trends Cell Biol. 2003; 13:484-92.
  • [2]Joly D, Ishibe S, Nickel C, Yu Z, Somlo S, Cantley LG. The polycystin 1-C-terminal fragment stimulates ERK-dependent spreading of renal epithelial cells. J Biol Chem. 2006; 281:26329-39.
  • [3]Boletta A. Emerging evidence of a link between the polycystins and the mTOR pathways. Pathogenetics. 2009; 2:6. BioMed Central Full Text
  • [4]Qian F, Wei W, Germino G, Oberhauser A. The nanomechanics of polycystin-1 extracellular region. J Biol Chem. 2005; 280:40723-30.
  • [5]Forman JR, Qamar S, Paci E, Sandford RN, Clarke J. The remarkable mechanical strength of polycystin-1 supports a direct role in mechanotransduction. J Mol Biol. 2005; 349:861-71.
  • [6]Nauli SM, Alenghat FJ, Luo Y, Williams E, Vassilev P, Li X et al.. Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nat Genet. 2003; 33:129-37.
  • [7]DeCaen PG, Delling M, Vien TN, Clapham DE. Direct recording and molecular identification of the calcium channel of primary cilia. Nature. 2013; 504:315-8.
  • [8]Streets AJ, Wagner BE, Harris PC, Ward CJ, Ong AC. Homophilic and heterophilic polycystin 1 interactions regulate E-cadherin recruitment and junction assembly in MDCK cells. J Cell Sci. 2009; 122:1410-7.
  • [9]Boca M, D’Amato L, Distefano G, Polishchuk RS, Germino GG, Boletta A. Polycystin-1 induces cell migration by regulating phosphatidylinositol 3-kinase-dependent cytoskeletal rearrangements and GSK3beta-dependent cell cell mechanical adhesion. Mol Biol Cell. 2007; 18:4050-61.
  • [10]Wilson PD, Geng L, Li X, Burrow CR. The PKD1 gene product, “polycystin-1,” is a tyrosine-phosphorylated protein that colocalizes with alpha2beta1-integrin in focal clusters in adherent renal epithelia. Lab Invest. 1999; 79:1311-23.
  • [11]Elliott J, Zheleznova NN, Wilson PD. c-Src inactivation reduces renal epithelial cell-matrix adhesion, proliferation, and cyst formation. Am J Physiol Cell Physiol. 2011; 301:C522-9.
  • [12]Gardel ML, Schneider IC, Aratyn-Schaus Y, Waterman CM. Mechanical integration of actin and adhesion dynamics in cell migration. Annu Rev Cell Dev Biol. 2010; 26:315-33.
  • [13]Mitra SK, Hanson DA, Schlaepfer DD. Focal adhesion kinase: in command and control of cell motility. Nat Rev Mol Cell Biol. 2005; 6:56-68.
  • [14]Ilic D, Furuta Y, Kanazawa S, Takeda N, Sobue K, Nakatsuji N et al.. Reduced cell motility and enhanced focal adhesion contact formation in cells from FAK-deficient mice. Nature. 1995; 377:539-44.
  • [15]Sieg DJ, Hauck CR, Schlaepfer DD. Required role of focal adhesion kinase (FAK) for integrin-stimulated cell migration. J Cell Sci. 1999; 112(Pt 16):2677-91.
  • [16]Turner CE. Paxillin and focal adhesion signalling. Nat Cell Biol. 2000; 2:E231-6.
  • [17]Subauste MC, Pertz O, Adamson ED, Turner CE, Junger S, Hahn KM. Vinculin modulation of paxillin-FAK interactions regulates ERK to control survival and motility. J Cell Biol. 2004; 165:371-81.
  • [18]Castelli M, Boca M, Chiaravalli M, Ramalingam H, Rowe I, Distefano G et al.. Polycystin-1 binds Par3/aPKC and controls convergent extension during renal tubular morphogenesis. Nat Commun. 2013; 4:2658.
  • [19]Outeda P, Huso DL, Fisher SA, Halushka MK, Kim H, Qian F et al.. Polycystin signaling is required for directed endothelial cell migration and lymphatic development. Cell Rep. 2014; 7:634-44.
  • [20]Yao G, Su X, Nguyen V, Roberts K, Li X, Takakura A et al.. Polycystin-1 regulates actin cytoskeleton organization and directional cell migration through a novel PC1-Pacsin 2-N-Wasp complex. Hum Mol Genet. 2014; 23:2769-79.
  • [21]Nickel C, Benzing T, Sellin L, Gerke P, Karihaloo A, Liu ZX et al.. The polycystin-1 C-terminal fragment triggers branching morphogenesis and migration of tubular kidney epithelial cells. J Clin Invest. 2002; 109:481-9.
  • [22]Boletta A, Qian F, Onuchic LF, Bhunia AK, Phakdeekitcharoen B, Hanaoka K et al.. Polycystin-1, the gene product of PKD1, induces resistance to apoptosis and spontaneous tubulogenesis in MDCK cells. Mol Cell. 2000; 6:1267-73.
  • [23]Ezratty EJ, Partridge MA, Gundersen GG. Microtubule-induced focal adhesion disassembly is mediated by dynamin and focal adhesion kinase. Nat Cell Biol. 2005; 7:581-90.
  • [24]Palamidessi A, Frittoli E, Ducano N, Offenhauser N, Sigismund S, Kajiho H et al.. The GTPase-activating protein RN-tre controls focal adhesion turnover and cell migration. Curr Biol. 2013; 23:2355-64.
  • [25]Rosse C, Boeckeler K, Linch M, Radtke S, Frith D, Barnouin K et al.. Binding of dynein intermediate chain 2 to paxillin controls focal adhesion dynamics and migration. J Cell Sci. 2012; 125:3733-8.
  • [26]Slack-Davis JK, Martin KH, Tilghman RW, Iwanicki M, Ung EJ, Autry C et al.. Cellular characterization of a novel focal adhesion kinase inhibitor. J Biol Chem. 2007; 282:14845-52.
  • [27]Etienne-Manneville S. Actin and microtubules in cell motility: which one is in control? Traffic. 2004; 5:470-7.
  • [28]Gardel ML, Sabass B, Ji L, Danuser G, Schwarz US, Waterman CM. Traction stress in focal adhesions correlates biphasically with actin retrograde flow speed. J Cell Biol. 2008; 183:999-1005.
  • [29]Boca M, Distefano G, Qian F, Bhunia AK, Germino GG, Boletta A. Polycystin-1 induces resistance to apoptosis through the phosphatidylinositol 3-kinase/Akt signaling pathway. J Am Soc Nephrol. 2006; 17:637-47.
  • [30]Karner CM, Chirumamilla R, Aoki S, Igarashi P, Wallingford JB, Carroll TJ. Wnt9b signaling regulates planar cell polarity and kidney tubule morphogenesis. Nat Genet. 2009; 41:793-9.
  • [31]Lienkamp SS, Liu K, Karner CM, Carroll TJ, Ronneberger O, Wallingford JB et al.. Vertebrate kidney tubules elongate using a planar cell polarity-dependent, rosette-based mechanism of convergent extension. Nat Genet. 2012; 44:1382-7.
  • [32]Wodarczyk C, Rowe I, Chiaravalli M, Pema M, Qian F, Boletta A. A novel mouse model reveals that polycystin-1 deficiency in ependyma and choroid plexus results in dysfunctional cilia and hydrocephalus. PLoS One. 2009; 4:e7137.
  • [33]Distefano G, Boca M, Rowe I, Wodarczyk C, Ma L, Piontek KB et al.. Polycystin-1 regulates extracellular signal-regulated kinase-dependent phosphorylation of tuberin to control cell size through mTOR and its downstream effectors S6K and 4EBP1. Mol Cell Biol. 2009; 29:2359-71.
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