Shank3: studio della regolazione genica metilazione dipendente e del ruolo nella struttura della sinapsi

Genetic and functional investigations conducted about the family of Gene Shank / ProSAP allow to describe in detail some aspects such as differential expression, the subcellular location and different interactions with proteins. This information provides the basis for deepen role of Shank in synapses and his involvement in the formation and remodeling of dendritic spines. Previous work has shown how overexpression of Shank3 in cells of the cerebellum is able to induce the formation of dendritic spines and functional synapses, whereas the inhibition of Shank3 in hippocampal neurons is able to reduce the number of dendritic spines. Overexpression of Shank1 in hippocampal neurons is able to acellerare maturation of dendritic spines. Is not yet clear whether Shank1, Shank2/ProSAP1, Shank3/ProSAP2 have specific roles or interchangeable in the synapse; Clarify any functional differences between these proteins lead to a greater understanding of the bases of operation of the CNS and the molecular basis of diseases characterized by mental retardation. Recent evidence showed the conservation of methylation of CpG islands in Shank3 during evolution, this suggests a role of methylation in expression regulation of Shank3. We proposed to characterize the Shank methylation of genes in different tissues and assess whether the DNA methylation was actually involved in the regulation of Shank3, we want to characterize the role of Shank3 in functioning of synapses with technology of siRNA.