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Tesi di dottorato in medicina >
Please use this identifier to cite or link to this item:
http://hdl.handle.net/2108/963
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| DC Field | Value | Language |
|---|
| contributor.advisor | Achsel, Tilmann | - |
| contributor.author | Di Penta, Alessandra | - |
| date.accessioned | 2009-07-30T13:13:02Z | - |
| date.available | 2009-07-30T13:13:02Z | - |
| date.issued | 2009-07-30T13:13:02Z | - |
| identifier.uri | http://hdl.handle.net/2108/963 | - |
| description | 19. ciclo | en |
| description.abstract | Spinal muscular atrophy (SMA) is the most common genetic cause of childhood disease and results
from selective loss of α motor neurons. SMA is caused by mutations or deletions of the telomeric
copy of the survival motor neuron 1 gene (SMN1). This gene is fundamental for the assembly and
regeneration of spliceosomal small nuclear ribonuclear proteins (snRNPs) in all cellular types. The
mechanism by which SMN deletion is responsible of selective neuro-muscular defect and specific
motor neurons degeneration is still unknown, even if some studies suggested an additional neuronspecific
function of the protein.
In this work, we investigated in neurons the role of SMN and LSm1 to LSm7, which is involved in
mRNA degradation in HeLa cells and may well require the SMN protein for assembly and/or
function.
We constructed stable neuroblastoma cell lines by RNA interference that express low level of SMN
protein and can be considered as a pathological model of SMA. We found that decreased expression
of SMN protein does not influence the assembly of snRNPs nor of the LSm1-7 complex. In these
cellular clones, LSm1 protein assembles in the cytoplasm as punctuated structures (P-bodies) that
are also found in control cells and all other cell types. Moreover, SMN knock-down clones showed
an atypical localization of heavy chain neurofilaments (NFH) that fuse in the soma. Overexpressing
SMN in wild type neuroblastoma (SH S5Y5) we observed the presence of aggregates in inclusion
bodies, suggesting the interaction between SMN and NFH. Even if SMN knock-down resemble the
pathological condition of SMA, the level of downregulated protein may be not enough to interfere
with the snRNPs biogenesis. We can speculate that in primary culture neurons exists a different
regulatory pathway. In fact, experiments on neurons from spinal cord, Purkinje cells and
hippocampal neurons demonstrated a mechanism of dendritic localization never seen in cell lines.
We showed for the first time that LSm1 protein, beside to localize in P-bodies in the soma, can
distribute on the dendrites in punctuate structures that contain no degradation enzymes such as
Dcp1a. Further, LSm1 binds specific dendritic mRNAs suggesting an involvement in the mRNA
transport and/or in the local protein synthesis.
In conclusion, we dimostrated that LSm1 can form new complexes with specific neuronal tasks and
hypothesize that the presence of SMN is crucial for the function of these complexes. | en |
| format.extent | 2294543 bytes | - |
| format.mimetype | application/pdf | - |
| language.iso | it | en |
| subject | snRNPs complex | en |
| subject | LSm1-7 complex | en |
| subject | SMN | en |
| subject | p-body | en |
| subject | mRNA transport | en |
| subject.classification | MED/26 Neurologia | en |
| title | Ruolo funzionale e localizzazione sub-cellulare delle proteine Sm e Sm-like nei neuroni | en |
| type | Doctoral thesis | en |
| degree.name | Neuroscienze | en |
| degree.level | Dottorato | en |
| degree.discipline | Facoltà di medicina e chirurgia | en |
| degree.grantor | Università degli studi di Roma Tor Vergata | en |
| date.dateofdefense | A.A. 2006/2007 | en |
| Appears in Collections: | Tesi di dottorato in medicina
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Description |
Size | Format |
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| TESI COMPLETA.pdf | | 2240Kb | Adobe PDF | View/Open |
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