Development, Signalling and Trafficking

Anne PLESSIS

Our work is at a point of overlap between developmental biology (the development of the wing in the fly, Drosophila melanogaster) and two major themes in cellular biology: signal transduction (of the morphogenic and oncogenic Hedgehog signal, HH) and intracellular trafficking of proteins. Our aim is to elucidate the mechanisms involved and to integrate these events in a cellular and developmental context.

 

 

+33 (0)157278044     anne.plessis (at) ijm.fr    

Our work is at a point of overlap between developmental biology (the development of the wing in the fly, Drosophila melanogaster) and two major themes in cellular biology: signal transduction (of the morphogenic and oncogenic Hedgehog signal, HH) and intracellular trafficking of proteins. Our aim is to elucidate the mechanisms involved and to integrate these events in a cellular and developmental context.

HH is involved in many developmental processes in animals and numerous carcinomas are associated with HH pathway deregulation. HH signal reception and transduction relies on two transmembrane proteins, Patched (Ptc) and Smoothened   factor called Cubitus interruptus (Ci)/GLI. Using high-throughput two-hybrid screens (collaboration with Hybrigenics), we previously identified novel interactions and interactors. We are currently using genetic, molecular and cellular techniques (in cultured cells and in flies) to study the role of three of these interactors. We thus hope to get a better understanding of HH transduction in Drosophila and, given the conservation of this pathway, also in Human – especially as concerns oncogenic pathologies.

Specific goals:
(i) Findings from our and other studies highlight the importance of membrane protein trafficking in the control of the HH pathway and in establishing the HH morphogenetic gradient. We want to determine in more detail the relationships between protein interactions, intracellular trafficking and post-translational changes involved in the transduction of the HH signal. We also intend to investigate how these various processes are regulated to produce different dose-dependent responses to HH. We are therefore characterizing novel phosphorylations of Smo and studying the ubiquitination of Ptc by two related ubiquitin-ligases of the NEDD4 family.
(ii) Our second project aims to provide a better understanding of the Ubiquitin-dependent processes that control the fate of Ci/GLI. We are studying the effect of a novel protein on the choice between degradation and cleavage of the transcription factor Ci.
(iii) Finally, in collaboration with Dr. R. Homlgren (Northwestern) we are seeking novel partners of HH signalling by combining the results of our two-hybrid screens with a genetic screen. We plan to complement these screens with a proteomic analysis of the proteins for which ubiquitination is regulated by HH.

Group Leader:

Anne PLESSIS
Téléphone : +33 (0)157278044
Email : anne.plessis (at) ijm.fr

 

Members:

Marina ANTUNES Biological engineer
Isabelle BECAM Researcher
Matthieu SANIAL Assistant biology engineer

 

Brigui AHofmann LArgüelles CSanial MHolmgren R and Plessis A.
Control of the dynamics and homeostasis of the Drosophila Hedgehog receptor Patched by two C2-WW-HECT-E3 Ubiquitin ligases. Open Biol. 2015 Oct;5(10).
Abstract

Bras S, Martin-Lannerée S, Gobert V, Augé B, Breig O, Sanial M, Yamaguchi M, Haenlin M, Plessis A, Waltzer L.. Myeloid leukemia factor is a conserved regulator of RUNX transcription factor activity involved in hematopoiesis. Proc Natl Acad Sci U S A2012 Mar 12.
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Farzan S. F., Ascano, A., Ogden S. K, Sanial M.Brigui A.Plessis A. and Robbins D. J. Costal2 Functions as a Microtubule-Dependent Motor in the Hedgehog Signal Transduction Pathway. Current Biology2008: 18,1-6.
Free Full Text

Claret S.Sanial M.,and Plessis A. Evidence for a novel positive feedback loop in the Hedgehog pathway: the seven transmembrane-domains protein Smoothened and the kinase Fused act on each other. Current Biology2007: 17, 1326-1333.
Free Full Text

Formstecher E, Aresta S, Collura V, Hamburger A, Meil A, Trehin A, Reverdy C, Betin V, Maire S, Brun C, Jacq B, Arpin M, Bellaiche Y, Bellusci S, Benaroch P, Bornens M, Chanet R, Chavrier P, Delattre O, Doye V, Fehon R, Faye G, Galli T, Girault JA, Goud B, de Gunzburg J, Johannes L, Junier MP, Mirouse V, Mukherjee A, Papadopoulo D, Perez F, Plessis A, Rosse C, Saule S, Stoppa-Lyonnet D, Vincent A, White M, Legrain P, Wojcik J, Camonis J, Daviet L.. Protein interaction mapping: a Drosophila case study. Genome Research2005: 15, 376-384.
Free Full Text

2015

Brigui AHofmann LArgüelles CSanial MHolmgren R and Plessis A.
Control of the dynamics and homeostasis of the Drosophila Hedgehog receptor Patched by two C2-WW-HECT-E3 Ubiquitin ligases. Open Biol. 2015 Oct;5(10).
Abstract

Kim, E. Y. Hsia, C. Brigui, A. Plessis A., Beachy P. A and Zheng X. The role of ciliary trafficking in Hedgehog receptor signaling. Sc. Signal.; (2015) Jun 2;8(379):ra55
Abstract

2014

Yanai H., Yoshioka Y., Yoshida H., Nakao Y., Plessis A. and Yamaguchi M.. Drosophila myeloid leukemia factor cooperates with DREF to activate the JNK signaling pathway. Oncogenesis (2014) 3:e98
Abstract

2013

Brunet T., Bouclet A., Ahmadi P., Mitrossilis D., Driquez B., Brunet A-C., Henry L., Serman F., Béalle G., Ménager C., Dumas-Bouchiat F., Givord D., Yanicostas C., Le-Roy D.,  M. Dempsey N., Plessis A. and Farge E.. Bilateria early mesoderm specification is determined by beta-catenin dependent mechanical induction. Nature Comm. (2013) 4:2821. Commentaires: Nature 504 (2013), “News and views” et http://www.knowtex.com/nav/quand-la-mecanique-controle-nos-genes_41307
Abstract

2012

Bras S, Martin-Lannerée S, Gobert V, Augé B, Breig O, Sanial M, Yamaguchi M, Haenlin M, Plessis A*, Waltzer L.* (* co-corresp. authors). Myeloid leukemia factor is a conserved regulator of RUNX transcription factor activity involved in hematopoiesis. Proc Natl Acad Sci U S A2012 109:4986-91
Free Full Text

S. Netter, C. Marchal, G. Vinatier, M. SanialA. Plessis, A.-M. Pret, L. Théodore and B. Limbourg-Bouchon; The HIV-1 Vpu Protein Induces Apoptosis in Drosophila via Activation of JNK Signaling. PLOS One2012 7: e34310.
Free Full Text

2008

Farzan S. F., Ascano, A., Ogden S. K, Sanial M., Brigui A., Plessis A. and Robbins D. J. Costal2 Functions as a Microtubule-Dependent Motor in the Hedgehog Signal Transduction Pathway. Current Biology 2008: 18,1-6.
Abstract

2007

Claret S., Sanial M.,and Plessis A. Evidence for a novel positive feedback loop in the Hedgehog pathway: the seven transmembrane-domains protein Smoothened and the kinase Fused act on each other. Current Biology 2007: 17, 1326-1333.
Abstract

2006

Malpel S., Claret S., Sanial M., Brigui A., Piolot T., Daviet L., Martin-Lannerée S. and  Plessis A. The last 59 amino acids of Smoothened cytoplasmic tail directly bind the protein kinase Fused and negatively regulate the Hedgehog pathway. Developmental Biology 2006:  303, 121-133.
Abstract

Dussillol F, Brissard-Zahraoui J. , Limbourg-Bouchon B., Boucher D., Fouix S., Lamour-Isnard C.,  Plessis A. and Busson D. Modulation of the Suppressor of fused protein regulates the Hedgehog signaling pathway in Drosophila embryo and imaginal discs. Developmental biology 291 (1): 53-66.

Martin-Lannerée S., Lasbleiz C., Sanial M., Fouix S., Besse F. and Plessis A.  Characterization of the Drosophila Myeloid Leukemia Factor. Genes to Cells 2006: 1317-35.
Abstract

2005

Formstecher E, Aresta S, Collura V, Hamburger A, Meil A, Trehin A, Reverdy C, Betin V, Maire S, Brun C, Jacq B, Arpin M, Bellaiche Y, Bellusci S, Benaroch P, Bornens M, Chanet R, Chavrier P, Delattre O, Doye V, Fehon R, Faye G, Galli T, Girault JA, Goud B, de Gunzburg J, Johannes L, Junier MP, Mirouse V, Mukherjee A, Papadopoulo D, Perez F, Plessis A, Rosse C, Saule S, Stoppa-Lyonnet D, Vincent A, White M, Legrain P, Wojcik J, Camonis J, Daviet L.. Protein interaction mapping: a Drosophila case study. Genome Research 2005 : 15, 376-384.
Abstract

2003

Fouix S., Martin-Lanérée S., Morla L., Sanial M., Lamour-Isnard C., Plessis A. Over-expression of a novel nuclear interactor of Suppressor of fused, the Drosophila myelodysplasia/myeloid leukaemia factor, induces abnormal morphogenesis associated with increased apoptosis and DNA synthesis. Genes to Cell 8: 897-911.

2002

Monnier. V., S. Ho K. S., Sanial M., Scott M. P. and Plessis A. Hedgehog signal transduction proteins: contacts of the Fused kinase and Ci transcription factor with the kinesin-related protein Costal2. BMC Developmental Biology 2: 4

1998

Monnier V., Dussillol F., Alves G., Lamour-Isnard C., and Plessis A. Suppressor of fused links Fused and Cubitus interruptus on the Hedgehog signalling pathway. Current Biology, 8: 583-586.

Therond P., Lamour-Isnard C., et Plessis A. Dissection moléculaire de la voie de transduction du signal Hedgehog. Médecine-Sciences 5; p 603-60.