期刊论文详细信息
BMC Cell Biology
GxcC connects Rap and Rac signaling during Dictyostelium development
Arjan Kortholt4  Peter JM Van Haastert4  Francisco Rivero3  Jetze Beeksma4  Fabrizia Fusetti2  Douwe Veltman1  Katarzyna Plak4 
[1] Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK;Department of Biochemistry, Netherlands Proteomics Centre, Groningen Biomolecular Sciences and Biotechnology Institute & Zernike Institute for Advanced Materials, University of Groningen, Groningen, AG, 9747, The Netherlands;Centre for Cardiovascular and Metabolic Research, The Hull York Medical School and Department of Biological Sciences, University of Hull, Hull, HU6 7RX, UK;Department of Cell Biochemistry, University of Groningen, Nijenborgh 7, Groningen, AG, 9747, The Netherlands
关键词: Dictyostelium;    Development;    GEF;    Rac;    Rap;   
Others  :  855516
DOI  :  10.1186/1471-2121-14-6
 received in 2012-09-20, accepted in 2013-01-25,  发布年份 2013
PDF
【 摘 要 】

Background

Rap proteins belong to the Ras family of small G-proteins. Dictyostelium RapA is essential and implicated in processes throughout the life cycle. In early development and chemotaxis competent cells RapA induces pseudopod formation by activating PI3K and it regulates substrate attachment and myosin disassembly via the serine/threonine kinase Phg2. RapA is also important in late development, however so far little is known about the downstream effectors of RapA that play a role in this process.

Results

Here we show that cells expressing constitutively active RapA exhibit a high level of Rac activation. With a pull-down screen coupled to mass spectrometry, we identified the Rac specific guanine nucleotide exchange factor, GxcC, as Rap binding partner. GxcC binds directly and specifically to active RapA and binds to a subset of Dictyostelium Rac proteins. Deletion studies revealed that this pathway is involved in regulating Dictyostelium development.

Conclusions

GxcC provides a novel link between Rap and Rac signalling and is one of the Rap effectors regulating the progression of multicellular development.

【 授权许可】

   
2013 Plak et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20140722034437333.pdf 2321KB PDF download
173KB Image download
58KB Image download
124KB Image download
87KB Image download
【 图 表 】

【 参考文献 】
  • [1]Bourne HR, Sanders DA, McCormick F: The GTPase superfamily: conserved structure and molecular mechanism. Nature 1991, 349:117-127.
  • [2]Nassar N, Horn G, Herrmann C, Scherer A, McCormick F, Wittinghofer A: The 2.2 A crystal structure of the Ras-binding domain of the serine/threonine kinase c-Raf1 in complex with Rap1A and a GTP analogue. Nature 1995, 375:554-560.
  • [3]Vetter IR, Wittinghofer A: The guanine nucleotide-binding switch in three dimensions. Science 2001, 294:1299-1304.
  • [4]Mitin N, Rossman KL, Der CJ: Signaling interplay in Ras superfamily function. Curr Biol 2005, 15:R563-R574.
  • [5]Xiong H, Rivero F: Assaying Rho GTPase-dependent processes in Dictyostelium discoideum. Methods Mol Biol 2012, 827:381-392.
  • [6]Noegel AA, Schleicher M: The actin cytoskeleton of Dictyostelium: a story told by mutants. J Cell Sci 2000, 113(Pt 5):759-766.
  • [7]Kessin RH: Evolutionary biology. Cooperation can be dangerous. Nature 2000, 408:917-919.
  • [8]Pan P, Hall EM, Bonner JT: Folic acid as second chemotactic substance in the cellular slime moulds. Nat New Biol 1972, 237:181-182.
  • [9]Bos JL: Linking Rap to cell adhesion. Curr Opin Cell Biol 2005, 17:123-128.
  • [10]Bos JL, de Rooij J, Reedquist KA: Rap1 signalling: adhering to new models. Nat Rev Mol Cell Biol 2001, 2:369-377.
  • [11]Kortholt A, Bolourani P, Rehmann H, Keizer-Gunnink I, Weeks G, Wittinghofer A, Van Haastert PJ: A Rap/phosphatidylinositol 3-kinase pathway controls pseudopod formation [corrected]. Mol Biol Cell 2010, 21:936-945.
  • [12]Kortholt A, Rehmann H, Kae H, Bosgraaf L, Keizer-Gunnink I, Weeks G, Wittinghofer A, Van Haastert PJ: Characterization of the GbpD-activated Rap1 pathway regulating adhesion and cell polarity in Dictyostelium discoideum. J Biol Chem 2006, 281:23367-23376.
  • [13]Jeon TJ, Lee DJ, Merlot S, Weeks G, Firtel RA: Rap1 controls cell adhesion and cell motility through the regulation of myosin II. J Cell Biol 2007, 176:1021-1033.
  • [14]Jeon TJ, Lee S, Weeks G, Firtel RA: Regulation of Dictyostelium morphogenesis by RapGAP3. Dev Biol 2009, 328:210-220.
  • [15]Parkinson K, Bolourani P, Traynor D, Aldren NL, Kay RR, Weeks G, Thompson CR: Regulation of Rap1 activity is required for differential adhesion, cell-type patterning and morphogenesis in Dictyostelium. J Cell Sci 2009, 122:335-344.
  • [16]Arthur WT, Quilliam LA, Cooper JA: Rap1 promotes cell spreading by localizing Rac guanine nucleotide exchange factors. J Cell Biol 2004, 167:111-122.
  • [17]Mun H, Jeon TJ: Regulation of actin cytoskeleton by Rap1 binding to RacGEF1. Mol Cells 2012, 54:71-76.
  • [18]de la Roche M, Mahasneh A, Lee SF, Rivero F, Cote GP: Cellular distribution and functions of wild-type and constitutively activated Dictyostelium PakB. Mol Biol Cell 2005, 16:238-247.
  • [19]Veltman DM, King JS, Machesky LM, Insall RH: SCAR knockouts in dictyostelium: WASP assumes SCAR’s position and upstream regulators in pseudopods. J Cell Biol 2012, 198:501-508.
  • [20]Mondal S, Neelamegan D, Rivero F, Noegel AA: GxcDD, a putative RacGEF, is involved in dictyostelium development. BMC Cell Biol 2007, 8:23. BioMed Central Full Text
  • [21]Raaijmakers JH, Bos JL: Specificity in Ras and Rap signaling. J Biol Chem 2009, 284:10995-10999.
  • [22]Kortholt A, van Haastert PJ: Highlighting the role of Ras and Rap during dictyostelium chemotaxis. Cell Signal 2008, 20:1415-1422.
  • [23]Herrmann C, Horn G, Spaargaren M, Wittinghofer A: Differential interaction of the ras family GTP-binding proteins H-Ras, Rap1A, and R-Ras with the putative effector molecules Raf kinase and Ral-guanine nucleotide exchange factor. J Biol Chem 1996, 271:6794-6800.
  • [24]Wohlgemuth S, Kiel C, Kramer A, Serrano L, Wittinghofer F, Herrmann C: Recognizing and defining true Ras binding domains I: biochemical analysis. J Mol Biol 2005, 348:741-758.
  • [25]Somesh BP, Vlahou G, Iijima M, Insall RH, Devreotes P, Rivero F: RacG regulates morphology, phagocytosis, and chemotaxis. Eukaryot Cell 2006, 5:1648-1663.
  • [26]Somesh BP, Neffgen C, Iijima M, Devreotes P, Rivero F: Dictyostelium RacH regulates endocytic vesicular trafficking and is required for localization of vacuolin. Traffic 2006, 7:1194-1212.
  • [27]Larochelle DA, Vithalani KK, De Lozanne A: A novel member of the rho family of small GTP-binding proteins is specifically required for cytokinesis. J Cell Biol 1996, 133:1321-1329.
  • [28]Rot G, Parikh A, Curk T, Kuspa A, Shaulsky G, Zupan B: DictyExpress: a dictyostelium discoideum gene expression database with an explorative data analysis web-based interface. BMC Bioinformatics 2009, 10:265. BioMed Central Full Text
  • [29]Veltman DM, Akar G, Bosgraaf L, Van Haastert PJ: A new set of small, extrachromosomal expression vectors for dictyostelium discoideum. Plasmid 2009, 61:110-118.
  • [30]Abramoff MD, Magalhaes PJ, Ram SJ: Image processing with ImageJ. Biophotonics International 2004, 11:36-42.
  文献评价指标  
  下载次数:37次 浏览次数:7次