Carlos Dotti
Neuronal Differentiation
VIB Department of Molecular and Developmental Genetics, K.U.Leuven
MD-PhD: National Univ. of Cordoba, Argentina, '84
Postdoc: Albany Medical Coll., Albany, NY, USA, '85-'88
Postdoc: EMBL, Heidelberg, Germany, '88-'90
Groupleader: EMBL, Heidelberg, Germany, '90-'00
Scientific Director: Cavalieri Ottolenghi Inst. of Neuroscience, Torino, Italy, '00-'05
VIB Group leader since 2005
e-mail: carlos.dotti@cme.vib-kuleuven.be
phone +32 16 34 72 32
address: Campus Gasthuisberg, Herestraat 49, box 602, 6th floor, 3000 Leuven, BELGIUM
Current team members
Group leader: Carlos Dotti
Postdoctoral scientists: Alejandro Omar Sodero, Annette Gärtner, Carina Weissmann, Joachim Schulz, Mauricio Martin, Patricia Aguirre, Silvia Menchòn, Tina Wahle
Ph.D. Students: Francesca Iannilli, Giulia Pollarolo, Laura Trovò, Leen Van Huffel
Visiting young scientist: Antonio Totaro
Support personnel: Christine Nys, Isabelle Lahousse, Krist'l Vennekens, Tatiana Estrada-Hernandez
Science, relevant to NERF
One of the goals of our group is to unravel the basic mechanisms of neuronal polarization, i.e. the position of axon and dendrites in a neuron. This process starts with the migration of the last post-mitotic neuroblasts from the germinal layer to their final destination in the cortical layer; the generation of short cytoplasmic extensions serving as sensors for the extracellular environment and a stop-signal to determine its final positioning. The accuracy of this process is of fundamental importance for the proper neuronal connectivity. To address this issue, we have largely relied on neuron differentiation experiments with rodent embryonic hippocampal neurons in vitro. The current project will study this process in an in situ environment using wild type as well as genetically modified mice and Drosophila melanogaster.
During aging, the plasma membrane of neurons undergoes significant changes in lipidic composition, including a moderate but significant loss of cholesterol and an increase in sphingomyelin. These changes are due to stress-activated increased transcription and surface mobilization of the cholesterol hydroxylating enzyme Cyp46 and the up-regulation of sphingomyelin synthase (1-3). Lipidic changes must necessarily affect plasma membrane rigidity and therefore the velocity and qualitative properties of proteins’ lateral diffusion, affecting downstream activities and therefore cell performance. It is our aim to define how lipidic modifications of the plasma membrane of aged cells affect neuronal function.
Potential interactions with NERF
We eludicate the molecular and biochemical mechanisms of restricted lateral diffusion of individual AMPA receptor subunits at synapses of aging neurons. The biological consequences for synaptic efficacy can be only deduced from previous biochemical work (i.e. reduced AMPA diffusion may reflect reduced insertion and thus less efficient LTP). Precise tools to directly visualize and measure, in space and time, single receptor lateral diffusion with electrical activity are required.
The picture shows live cell analysis and computer reconstruction of path followed by single recorded AMPA receptors (1000 frames, one frame each 74 msec).
Selected publications
- Martin, M., Perga, S., Trovo, L., Rasola, A., Holm, P., Rantamäki, T., Harkany, T., Castrén, E., Chiara, F. and Dotti, C.G. (2008) Cholesterol loss enhances TrkB signaling in aging hippocampal neurons. Mol. Biol. of the Cell 19: 2001-2012
- Schmidt M, Maritzen T, Kukhtina V, Higman V, Doglio L, Barak N, Strauss H, Oschkinat H, Dotti C, Haucke V
Regulation of endosomal membrane traffic by a Gadkin/AP-1/kinesin KIF5 complex
P NATL ACAD SCI USA e-pub, e-pub, 2009
- Calderon De Anda F, Gärtner A, Tsai L, Dotti C
Pyramidal neuron polarity axis is defined at the bipolar stage
J CELL SCI 121, 178-85, 2008
- Schubert V, Da Silva J, Dotti C
Localized recruitment and activation of RhoA underlies dendritic spine morphology in a glutamate receptor-dependent manner
J CELL BIOL 172, 453-67, 2006
- Calderon De Anda F, Pollarolo G, Santos Da Silva J, Camoletto g, Feiguin F, Dotti C
Centrosome localization determines neuronal polarity
NATURE 436, 704-708, 2005
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