Cell migration and invasion require the dynamic coordination of adhesion, cytoskeletal organization, as well as protein and membrane traffic at the leading edge of the cell. Similar processes are involved in the migration of growth cones and in the establishment of synapses during neuronal development. Our major interest is the identification and analysis of the molecular mechanisms driving the protrusive activity at the edge of migrating cells and in developing neurons. We have identified novel molecular networks that are implicated in these processes. These networks include scaffold proteins, regulators and effectors of small GTPases of the Rho and Arf families. By using both in vitro and in vivo approaches, we are aiming at characterizing fundamental cellular mechanisms underlying cell motility events relevant to both physiological and pathological conditions.
A second line of research is on the mechanisms that drive the development and function of cortical GABAergic interneurons. We use transgenic mice with knockout for Rac GTPases in combination with a novel protocol to obtain long-term cultures of purified interneurons from WT and KO animals, which has been recently setup in the laboratory. These experimental systems are used in parallel to address the molecular mechanisms that drive the development of functional inhibitory networks within the brain, and are relevant to neuropsychiatric diseases.
Sala K, Raimondi A, Tonoli D, Tacchetti C, de Curtis I. Identification of a membrane-less compartment regulating invadosome function and motility. Sci Rep. 2018; 8:1164.
Franchi SA, Macco R, Astro V, Tonoli D, Savino E, Valtorta F, Sala K, Botta M, de Curtis I. A Method to Culture GABAergic Interneurons Derived from the Medial Ganglionic Eminence. Front Cell Neurosci. 2018; 11:423.
Franchi SA, Astro V, Macco R, Tonoli D, Barnier JV, Botta M, de Curtis I. Identification of a Protein Network Driving Neuritogenesis of MGE-Derived GABAergic Interneurons. Front Cell Neurosci. 2016; 10: 289.
Astro V, Tonoli D, Chiaretti S, Badanai S, Sala K, Zerial M, de Curtis I. Liprin-α1 and ERC1 control cell edge dynamics by promoting focal adhesion turnover. Sci Rep. 2016; 6: 33653.
Pennucci R, Talpo F, Astro V, Montinaro V, Morè L, Cursi M, Castoldi V, Chiaretti S, Bianchi V, Marenna S, Cambiaghi M, Tonoli D, Leocani L, Biella G, D'Adamo P, de Curtis I. Loss of Either Rac1 or Rac3 GTPase Differentially Affects the Behavior of Mutant Mice and the Development of Functional GABAergic Networks. Cereb Cortex. 2016 Feb;26(2):873-890.
Astro V, de Curtis I. Plasma membrane-associated platforms: dynamic scaffolds that organize membrane-associated events. Science Signal. 2015 Mar 10;8(367):re1.
Vaghi V, Pennucci R, Talpo F, Corbetta S, Montinaro V, Barone C, Croci L, Spaiardi P, Consalez GG, Biella G, de Curtis I. Rac1 and Rac3 GTPases Control Synergistically the Development of Cortical and Hippocampal GABAergic Interneurons. Cereb Cortex. 2014 May;24(5):1247-58.
Astro V, Asperti C, Cangi MG, Doglioni C, de Curtis I. Liprin-α1 regulates breast cancer cell invasion by affecting cell motility, invadopodia and extracellular matrix degradation. Oncogene 2011 Apr 14;30(15):1841-9.
Asperti C, Astro V, Totaro A, Paris S, de Curtis I. Liprin-alpha1 promotes cell spreading on the extracellular matrix by affecting the distribution of activated integrins. J. Cell Sci. 2009 Sep 15;122(Pt 18):3225-32.
Corbetta S, Gualdoni S, Ciceri G, Monari M, Zuccaro E, Tybulewicz VL, de Curtis I. Essential role of Rac1 and Rac3 GTPases in neuronal development. FASEB J. 2009 May;23(5):1347-57.
Di Cesare A, Paris S, Albertinazzi C, Dariozzi S, Andersen J, Mann M, Longhi R, de Curtis I. p95-APP1 links membrane transport to Rac-mediated reorganization of actin. Nature Cell Biol. 2000 Aug;2(8):521-30.
Albertinazzi C, Gilardelli D, Paris S, Longhi R, de Curtis, I. Overexpression of a neural-specific Rho family GTPase, cRac1B, selectively induces enhanced neuritogenesis and neurite branching in primary neurons. J. Cell Biol. 1998 Aug 10; 142(3): 815–825.