M. Isabel Geli: The endocytic pathway and the actin cytoskeleton
Our subline aims to unveil the molecular mechanisms supporting endocytic traffic with a particular focus in the role that actin plays in the process. In addition, we intend to identify the proteins that adapt endocytic traffic to the complex physiological roles it plays in high eukaryotes. For these purposes, we use S. cerevisiae as a model system to dissect the basic molecular mechanisms involved in endocytic budding from the plasma membrane. By combining the powerful yeast genetics with informative in vitro assays, monitoring of single endocytic events by life-cell fluorescence microscopy and sophisticated ultrastructural analysis, we provide experimental data to refine molecular models explaining the process. Interaction of the lipid bilayer with proteins capable of inducing membrane curvature, assembly of the clathrin coat, rearrangement and modification of lipids and forces provided by localized Arp2/3-dependent actin polymerization and the mechanochemical activity of myosins are the focus of our research. In a complementary approach, we have used functional genomics in mammalian cultured cells to identify human genes, not present in unicellular organisms such as S. cerevisiae, which contribute to the fine tuning of the complex physiological functions of endocytosis in higher eukaryotes.
Articles from the group
- F. Z. Idrissi, A. Blasco, A. Espinal and M. I. Geli (2012) "Ultrastructural dynamics of proteins involved in endocytic budding"Proc. Natl Acad Sci USA. Sept 4. [Epub ahead of print].
- H. Grötsch, J. P. Giblin, F.-Z. Idrissi, I.-M. Fernandez-Golbano, J. R. Collette, T. M. Newpher, V. Robles, S. K. Lemmon and M. I. Geli. (2010) "Calmodulin dissociation modulates Myo5 recruitment and function at endocytic sites" EMBO J. 29: 2899-914.
- F.-Z. Idrissi, H. Grötsch, I. M. Fernández-Golbano, C. Presciatto-Baschong, H. Riezman and M. I. Geli. (2008) “ Distinct acto/myosin-I structures associate with endocytic profiles at the plasma membrane” J. Cell Biol. 180: 1219-32. B. L. Großhans, H. Grötsch, D. Mukhopadhyay+, I. M. Fernández, J. Pannsfield, F.-Z.
- Idrissi, J. Lechner, H. Riezman and M. I. Geli (2006) “TEDS site phosphorylation of the yeast myosins-I is required for ligand-induced but not for constitutive endocytosis of the G protein-coupled receptor Ste2p”. J. Biol. Chem. 281, 11104-14.
- B. Schmelzl, and M. I Geli (2002) “An efficient genetic screen in mammalian cultured cells” EMBO Rep. 3, 683-87. F.Z.
- Idrissi, B.L. Wolf, and M.I. Geli (2002) “Cofilin, but not profilin, is required for Myosin-I-induced actin polymerization and the endocytic uptake in yeast” Mol. Biol. Cell. 13, 4074-87.
- M. I. Geli*, B. Schmelzl, R. Lombardi, and H. Riezman (2000) “An intact SH3 domain is required for myosin-I induced actin polymerization” EMBO J. 19, 4281-91. * Corresponding author.
Articles from the group in collaboration with other research teams
- Collette JR, Chi RJ, Boettner DR, Fernandez-Golbano IM, Plemel R, Merz AJ, Geli MI, Traub LM, Lemmon SK. (2009) Clathrin functions in the absence of the terminal domain binding site for adaptor-associated clathrin-box motifs. Mol Biol Cell. 14: 3401-13.
- A. C. De Luca, G. Volpe, A. Morales Drets, M. I. Geli, G. Pesce, G. Rusciano, A. Sasso, D. Petrov (2007). “Real-time actin-cytoskeleton depolymerization detection in a single cell using optical tweezers”. Optic Express. (2007) 15, 7922-7932.
- G. P. Singh, G. Volpe, C. M. Creely, H. Grötsch, I. M. Geli and D. Petrov (2006) ''The lag phase and G1 phase of a single yeast cell monitored by Raman microspectroscopy'' J. of Raman Spec. 37, 858-864.
- T. Newpher, F. Z. Idrissi, M. I. Geli and S. K. Lemmon (2006) “Novel Function of Clathrin Light Chain in Promoting Endocytic Vesicle Formation” Mol. Biol. Cell. 17:4343-52.
- J. S. Chang, K. Henry, M. I. Geli and S. K. Lemmon (2006) “Cortical Recruitment and Nuclear-Cytoplasmic Shuttling of Scd5p, a Protein Phosphatase- 1 Targeting Protein Involved in Actin Organization and Endocytosis”. Mol. Biol. Cell. 17:251-62.J.S.
- Chang, K. Henry, B.L. Wolf, M. I. Geli, and S.K. Lemmon (2002) “Protein phosphatase-1 binding to scd5p is important for regulation of actin organization and endocytosis in yeast” J. Biol. Chem. 277:48002-8.
Other selected contributions from the principal investigator
- M. I. Geli, A. Wesp and H. Riezman (1998) "Distinct functions of calmodulin are required for the uptake step of receptor mediated-endocytosis in yeast: the type I myosin Myo5p is one of the calmodulin targets" EMBO J. 17, 635-47.
- M. I. Geli and H. Riezman (1996) "Role of type I myosins in receptor-mediated endocytosis in yeast" Science 272, 533-5.
- M. I. Geli, M. Torrent and D. Ludevid (1994) "Two structural domains mediate two sequential events in g-Zein targeting: protein endoplasmic reticulum retention and protein body formation" Plant Cell 6, 1911-22.
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Ministerio de Ciencia e Innovación: BFU2008-03500: Actin-dependent endocytosis
Ministerio de Educación y Ciencia: BFU2005-04089: Estudio de la endocitosis asociada a rafts lipídicos
Ministerio de Ciencia y Tecnología: SAF2002-04707: Estudio de la endocitosis asociada a rafts lipídicos
Deustche Forschungsgemeinschaft: SPP 1068, Molecular Motors
Deustche Forschungsgemeinschaft: SFB 352, Molecular Mechanisms of the Intracellular Transport Processes