Data di Pubblicazione:
2009
Citazione:
Eps8 regulates axonal filopodia in hippocampal neurons in response to BDNF / E. Menna, A. Disanza, C. Cagnoli, U. Schenk, G. Gelsomino, E. Frittoli, M. Hertzog, N. Offenhauser, C. Sawallisch, H.J. Kreienkamp, F.B. Gertler, P.P. Di Fiore, G. Scita, M. Matteoli. ((Intervento presentato al convegno ABCD Meeting: Membrane trafficking and organelle biogenesis tenutosi a Bertinoro nel 2009.
Abstract:
The regulation of filopodia plays a crucial role during neuronal development and
synaptogenesis. Axonal filopodia, which are known to originate presynaptic
specializations, are regulated in response to neurotrophic factors. The structural
components of filopodia are actin filaments, whose dynamics and organization are
controlled by ensembles of actin binding proteins. How neurotrophic factors regulate
these latter proteins remains, however, poorly defined.
Here, using a combination of mouse genetic, biochemical and cell biological assays,
we show that genetic removal of Eps8, an actin-binding and regulatory protein
enriched in the growth cones and developing processes of neurons, significantly
augments the number and density of VASP-dependent axonal filopodia. The
reintroduction of Eps8 WT, but not an Eps8 capping-defective mutant into primary
hippocampal neurons restored axonal filopdia to wild type levels. We further show
that the actin barbed end capping activity of Eps8 is inhibited by BDNF treatment
through MAPK-dependent phosphorylation of Eps8 residues S624 and T628.
Additionally, an Eps8 mutant, impaired in the MAPK target sites (S624A/T628A),
displays increased association to actin-rich structures, is resistant to BDNF-mediated
release from microfilaments, and inhibits BDNF-induced filopodia. The opposite is
observed for a phosphomimetic Eps8 (S624E/T628E) mutant.
Thus, collectively, our data identify Eps8 as a critical capping protein in the
regulation of axonal filopodia and delineate a molecular pathway by which BDNF,
through MAPK-dependent phosphorylation of Eps8, stimulates axonal filopodia
formation, a process with crucial impacts on neuronal development and synapse
formation.
Tipologia IRIS:
14 - Intervento a convegno non pubblicato
Elenco autori:
E. Menna, A. Disanza, C. Cagnoli, U. Schenk, G. Gelsomino, E. Frittoli, M. Hertzog, N. Offenhauser, C. Sawallisch, H.J. Kreienkamp, F.B. Gertler, P.P. Di Fiore, G. Scita, M. Matteoli
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