Parkin is responsible for the vast majority of the Autosomal Recessive Juvenile Parkinsonism (Kitada et al., 1998), an atypical form of Parkinson’s Disease (PD) with early onset. Parkin is an ubiquitin E3 ligase (Shimura et al., 2000), catalyzing the addition of ubiquitin to target proteins, and therefore it is involved in the protein quality control and in the cellular cleaning system. Furthermore, it is already reported that parkin is able to associate with (Ren et al., 2003) and to modulate the stability (Yang et al., 2005) of microtubules (MTs), cytoskeletal elements involved in cell shape control and axonal transport processes. Nevertheless, nothing is known about the capacity of parkin to regulate -tubulin PTMs, that are usually used as marker of MTs with different stability and that, recently, have been directly linked to neurodegenerative processes (Rogowski et al., 2010). Moreover, until now there are no evidences that parkin is involved in the regulation of axonal transport, a MT-dependent function implicated in neurodegenerative processes (Morfini et al., 2009). Therefore, here we analyze -tubulin PTMs and axonal transport in mice lacking parkin, and we observe that alteration of MT stability is present in knockout mice and it is associated to defects of organelle transport. These data suggest a new physiological role for parkin, and because many PD-linked proteins, as parkin, -synuclein and leucine-rich repeat kinase 2, impact MT organization and stability, the pivotal role of MT dysfunction in PD etiopathogenesis is a well sustained and concrete hypothesis.
|Titolo:||Parkin absence impacts microtubule stability and axonal transport in knockout mice|
|Data di pubblicazione:||mag-2011|
|Parole Chiave:||Parkin ; Microtubule Stability ; Axonal Transport|
|Settore Scientifico Disciplinare:||Settore BIO/06 - Anatomia Comparata e Citologia|
Settore BIO/16 - Anatomia Umana
|Citazione:||Parkin absence impacts microtubule stability and axonal transport in knockout mice / D. Cartelli, J. Sassone, A. Amadeo, A. Ciammola, G. Cappelletti. ((Intervento presentato al 5. convegno Meeting on the Molecular Mechanism of Neurodegeneration tenutosi a Milano nel 2011.|
|Appare nelle tipologie:||14 - Intervento a convegno non pubblicato|