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| | [[image:Cover_web_page_OpenWetWarebis.tif]] |
| [[Image:CoverLeBorgne.jpg]] | | <div style="padding: 20px; color: #ffffff; background-color: #000; width: 1045px"> |
| ==Contact Info== | | <center> |
| *'''Roland Le Borgne'''
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| *CNRS UMR 6061
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| *Institut de Génétique et Développement-IGDR
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| *Faculté de Médecine
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| *2 avenue du Pr Bernard
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| *35000 Rennes
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| *France
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| *''roland.leborgne@univ-rennes1.fr''
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| *phone: 33 223234894/0686058923
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| [[Image:LeBorgne1.jpg]]
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| ==Education== | | [[LeBorgne| <font face="Helvetica" style="color:#ffffff"> '''Home''' </font>]] |
| <!--Include info about your educational background--> | | [[LeBorgne:Contact | <font face="Helvetica" style="color:#faf342"> '''Contact''' </font>]] |
| * 1995, PhD, EMBL-Heidelberg Germany
| | [[LeBorgne:Back Door | <font face="Helvetica" style="color:#faf342"> '''Position/news''' </font>]] |
| * 2005 HDR, University de Rennes
| | [[LeBorgne:Lab Members | <font face="Helvetica" style="color:#faf342"> '''Lab Members''' </font>]] |
| | [[LeBorgne:Publications | <font face="Helvetica" style="color:#faf342"> '''Publications''' </font>]] |
| | [[LeBorgne:Research | <font face="Helvetica" style="color:#faf342"> '''Research''' </font>]] |
| | [[LeBorgne:Collaborators | <font face="Helvetica" style="color:#faf342"> '''Collaborators''' </font>]] |
| | [[LeBorgne:Talks | <font face="Helvetica" style="color:#faf342"> '''Useful links''' </font>]] |
| | </center> |
| | </div><br> |
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| ==Research interests==
| | The team was created in 2006 thanks to the CNRS ATIP programme 'Developmental Cell Biology' |
| <!-- Feel free to add brief descriptions to your research interests as well -->
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| # Asymmetric cell division is a conserved mechanism by which cell fate diversity is generated during Metazoan development1. How one cell can generate two daughter cells with different identities and how defects in this asymmetry can contribute to cancer are the fundamental questions we are addressing in Drosophila. We are investigating this process in the context of asymmetric cell division of neural precursor cells, called Sensory Organ Precursor (SOP)1,2. These latter undergo four rounds of asymmetric divisions, in which mother cells generate distinct daughters via the unequal segregation of the cell-fate determinants Numb and Neuralized at mitosis. At each division binary cell fate decision are regulated by Delta-Notch dependent cell-cell signalling. Numb is an endocytic protein that can bind to Notch and a four pass transmembrane protein named Sanpodo (Spdo), a protein required for Notch activation in SOP lineage, thereby preventing Notch activation in this cell2. Neur acts in SOPs and pIIb cells to regulate the endocytosis and signalling activity of Dl, thereby promoting N activation in non-SOP (lateral inhibition) and pIIa cells (binary cell fate decision), respectively2. Despite intensive studies, the mechanism whereby Neur regulates Dl activity is not known. Two non-exclusive models have been proposed to explain the role of ubiquitin-dependent endocytosis of Dl in Notch receptor activation. First, the ‘pulling’ model proposes that internalization of Dl bound to its receptor exerts pulling forces on Notch and induces a conformational change exposing the S2 cleavage site to metalloproteases. Alternatively, the ‘activation/recycling’ model proposes that internalization is required to promote the formation of active ligands that are recycled back to the cell surface to activate Notch1. However the nature of the ligand activation and the subcellular localisation where recycled Dl could interact with Notch to produce signalling remained unknown. Our research aims to understand how intracellular trafficking contributes to the definition of the polarity axis of the divisions and ensure the proper spatio-temporal regulation of Notch-dependent fate decision.
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| # Interest 2
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| # Interest 3
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| ==Publications==
| | and is hosted within the Institute of Genetic and Development (Rennes, France): *[http://igdr.univ-rennes1.fr/ Institut de Génétique et Développement de Rennes] |
| <!-- Replace the PubMed ID's ("pmid=#######") below with the PubMed ID's for your publications. You can add or remove lines as needed -->
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| <biblio>
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| #1- Najate Benhra , Françoise Vignaux, Aurore Dussert, François Schweisguth and Roland Le Borgne (2010) Neuralized promotes basal to apical transcytosis of Delta in epithelial cells MBC 21, 2078-86
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| //cover picture
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| // Cited in Faculty of 1000 Biology
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| #2- Dif A, Boulmedais F, Pinot M, Roullier V, Baudy-Floc'h M, Coquelle FM, Clarke S, Neveu P, Vignaux F, Le Borgne R, Dahan M, Gueroui Z, Marchi-Artzner V (2009) Small and stable peptidic PEGylated quantum dots to target polyhistidine-tagged proteins with controlled stoichiometry J. am. Chem. Soc. 131(41):14738-46.
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| #3- Michaux G, Le Borgne R.
(2009)Tri sélectif et recyclage : Wntless et le retromer, deux acteurs clés de la signalisation WNT [Sorting, recycling and WNT signaling: Wntless and retromer functions.].
Med. Sci. (Paris), 25(6-7):617-621.
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| #4- Smith CA, Lau KM, Rahmani Z, Dho SE, Brothers G, She YM, Berry DM, Bonneil E, Thibault P, Schweisguth F, Le Borgne R, McGlade CJ. (2007) aPKC-mediated phosphorylation regulates asymmetric membrane localization of the cell fate determinant Numb. EMBO J. 2007 Jan 24;26(2):468-80
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| // Cited in Faculty of 1000 Biology
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| #5- Le Borgne,R. (2006). Regulation of Notch signalling by endocytosis and endosomal sorting. Curr Opin Cell Biol. 18(2), 213-22
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| #6- Langevin,L., Le Borgne,R., (equal contribution), Rosenfeld, F., Gho,M., Schweisguth, F. and Bellaïche, Y. (2005). Lethal giant larvae controls the localisation of the Notch signalling regulators Numb, Neuralized and Sanpodo in Drosophila sensory organ precursor cells. Current Biology 15, 955-62
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| // Cited in Faculty of 1000 Biology
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| #7- Le Borgne, R., Bardin, A. and Schweisguth F. (2005) Roles of receptor and ligand endocytosis in the regulation of Notch signaling. Development 132, 1751-62
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| #8- Le Borgne, R., Remaud, S., Hamel,S., and Schweisguth F (2005). The E3 ubiquitin ligases Mind bomb and Neuralized have distinct and complementary functions in the regulation of Delta and Serrate activity in drosophila. PLoS Biology 3, e96
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| // Cited in Faculty of 1000 Biology
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| #9- Bardin, A.J., Le Borgne, R., Schweisguth F. (2004). Asymmetric localization and function of cell-fate determinants: a fly's view. Curr Opin Neurobiol. Feb;14(1):6-14
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| #10- Le Borgne, R. and Schweisguth, F. (2003). Unequal segregation of Neuralized biases Notch activation during asymmetric cell division. Developmental Cell 5(1), 139-148
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| // Cited in Faculty of 1000 Biology | |
| #11- Le Borgne, R. and Schweisguth, F. (2003). Notch signaling: endocytosis makes Delta signal better. Curr. Biol. 23, R273-R275
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| #12- Morel V., Le Borgne R. and Scweisguth F.(2003). Snail is required for Delta endocytosis and Notch-dependent activation of single-minded expression in Drosophila. Development,Genes and Evolution.213 (2), 65-72.
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| #13- Le Borgne R., Bellaïche Y.and Schweisguth F.(2002) Drosophila E-Cadherin regulates the orientation of asymetric cell division in the sensory organ lineage, Current Biology, 12, 95-104
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| #14- Ben-Yaacov, S., Le Borgne, R., Abramson, I., Schweisguth,F. , and Schejter, E. D. (2001). Wasp, The Drosophila Wiskott-Aldrich Syndrome Gene Homolog, Is Required For Cell Fate Decisions Mediated By Notch Signaling . J. Cell Biol. 152, 1-13
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| #15- Waguri, S., Dewitte, F., Le Borgne, R., Rouille, Y., Uchiyama, Y., Dubremetz JF, and Hoflack, B. (2003). Visualization of TGN to Endosome Trafficking through Fluorescently Labeled MPR and AP-1 in Living Cells. Mol Biol Cell. 14(1):142-55
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| // Cited in Faculty of 1000 Biology | |
| #16- Le Borgne, R., Martin, P., Planque, N., De Witte, F., Saule, S., and Hoflack, B. (2001).The AP-3 dependent targeting of the melanosomal glycoprotein QNR71 requires its di-leucine-based sorting signal. J. Cell Sci. 114, 2831-41
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| #17- Le Borgne, R. and Hoflack, B. (1998). Mechanisms of protein sorting and coat assembly: insights from the clathrin-coated vesicle pathway. Curr. Opin. Cell Biol. 10: 499-503
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| #18- Le Borgne, R., Alconada, A., Bauer, U., and Hoflack, B. (1998). The mammalian AP-3 adaptor-like complex mediates the intracellular transport of lysosomal membrane glycoproteins. J. Biol. Chem. 273: 29451-29461
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| #19- Le Borgne, R., and Hoflack, B. (1998). Protein transport from the secretory to the endocytic pathway in mammalian cells. Bioch. Biophys. Acta: thematic Issue on « The Golgi Complex », 1404: 195-209
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| #20- Distel, B., Bauer, U., Le Borgne,R., and Hoflack, B. (1998). Basolateral sorting of the cation-dependent mannose 6-phosphate receptor in Madin-Darby Canine Kidney cells: identification of a basolateral determinant unrelated to clathrin-coated pit localization signals. J. Biol. Chem. 273: 186-193
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| #21- Le Borgne,R., and Hoflack,B. (1997). The mannose 6-phosphate receptors regulate the formation of clathrin-coated vesicles in the trans-Golgi network. J. Cell Biol. 137: 335-345
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| #22- Salamero,J., Le Borgne,R., Saudrais,C., Goud,B., and Hoflack,B. (1996). Expression of major histocompatibility complex class II molecules in HeLa cells promotes the recruitment of AP-1 Golgi-specific assembly proteins on Golgi membranes. J. Biol. Chem. 271: 30318-30321
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| #23- Mauxion,F., Le Borgne,R., Munier-Lehmann,H., and Hoflack,B. (1996). A casein kinase II phosphorylation site in the cytoplasmic domain of the cation-dependent mannose 6-phosphate receptor determines the high affinity interaction of the AP-1 Golgi-assembly proteins with membranes. J. Biol. Chem. 271: 2171-2178
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| #24- Le Borgne,R., Griffiths,G., and Hoflack,B. (1996). Mannose 6-phosphate receptors and ADP-ribosylation factors cooperate for high affinity interaction of the AP-1 Golgi-assembly proteins with membranes. J. Biol. Chem. 271: 2162-2170
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| #25- Mauxion,F., Schmidt,A., Le Borgne,R., and Hoflack,B. (1995). Chimeric proteins containing the cytoplasmic domains of the mannose 6-phosphate receptors codistributes with the endogenous receptors. European J. Cell Biol. 66: 119-126
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| #26- Ludwig,T., Le Borgne,R., and Hoflack,B. (1995). Roles for mannose 6-phosphate receptors in lysosomal emzyme sorting, IGF-II binding and clathrin-coat assembly. Trends in Cell Biol. 5: 202-206
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| #27- Le Borgne, R., Schmidt,A., Mauxion,F., Griffiths,G., and Hoflack,B. (1993). Binding of AP-1 Golgi adaptors to membranes requires phosphorylated cytoplasmic domains of the mannose 6-phosphate/insulin-like growth factor II receptor. J. Biol. Chem. 268: 22552-22556
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| #28- Andréoli,C., Martin,M., Le Borgne,R., Reggio,H., and Mangeat,P. (1994). Ezrin has properties to self-associate at the plasma membrane. J. Cell Science 107: 2509-2521
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| #29- Gaillet, S., Alonso, G., Le Borgne, R., Barbanel, G., Malaval, F., Assenmacher, I., Szafarczyk, A.(1993). Effects of discrete lesions in the ventral noradrenergic ascending bunDeltae on the corticotropic stress response depend on the site of the lesion and on the plasma levels of adrenal steroids. Neuroendocrinology 58: 408-419
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| </biblio>
| | Main interests: |
| | | [[Image:Numb-1.jpg|thumb|Unequal segregation of Numb (red) in dividing SOP, tubulin (green)]] |
| ==Useful links==
| | Asymmetric cell division is a conserved mechanism by which cell fate diversity is generated during Metazoan development. How one cell can generate two daughter cells with different identities and how defects in this asymmetry can contribute to cancer are the fundamental questions we are addressing in Drosophila. We are investigating this process in the context of asymmetric cell division of neural precursor cells, called Sensory Organ Precursor (SOP). These latter undergo four rounds of asymmetric divisions, in which mother cells generate distinct daughters via the unequal segregation of the cell-fate determinants Numb and Neuralized at mitosis. At each division binary cell fate decision are regulated by Delta-Notch dependent cell-cell signalling. Numb is an endocytic protein that can bind to Notch and a four pass transmembrane protein named Sanpodo (Spdo), a protein required for Notch activation in SOP lineage, thereby preventing Notch activation in this cell. Neur acts in SOPs and pIIb cells to regulate the endocytosis and signalling activity of Dl, thereby promoting N activation in non-SOP (lateral inhibition) and pIIa cells (binary cell fate decision), respectively. Despite intensive studies, the mechanism whereby Neur regulates Dl activity is not known. Two non-exclusive models have been proposed to explain the role of ubiquitin-dependent endocytosis of Dl in Notch receptor activation. First, the ‘pulling’ model proposes that internalization of Dl bound to its receptor exerts pulling forces on Notch and induces a conformational change exposing the S2 cleavage site to metalloproteases. Alternatively, the ‘activation/recycling’ model proposes that internalization is required to promote the formation of active ligands that are recycled back to the cell surface to activate Notch1. However the nature of the ligand activation and the subcellular localisation where recycled Dl could interact with Notch to produce signalling remained unknown. Our research aims to understand how intracellular trafficking contributes to the definition of the polarity axis of the divisions and ensure the proper spatio-temporal regulation of Notch-dependent fate decision. |
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