SUMO-PCDH10 PROJECT
OUR RESEARCH
We aim to find a link between autism and sumoylation
WHAT IS AUTISM SPECTRUM DISORDER?
Autism Spectrum Disorder (ASD) is a severe and complex neuropsychiatric disorder characterized by impaired social behaviour and Intellectual Disability (ID) in up to 70% of the cases. ASD affects millions of individuals worldwide and represents a major health and economic burden in the modern society. Although there has been much research interest in uncovering the molecular mechanisms that are responsible for ASD, to date there is no effective therapy.
At the molecular level, ASD is characterized by altered neuronal signalling that contributes to synaptic dysfunctions. Here, we identified the ASD-related protein Protocadherin-10 (PCDH10) as a novel target of sumoylation.
WHY SUMOYLATION IS SO IMPORTANT IN NEURONS?
Sumoylation consist in the covalent but reversible conjugation of the Small Ubiquitin-like MOdifier (SUMO) protein to specific lysine residues of target proteins. In neurons, sumoylation regulates a wide range of cellular functions, including spinogenesis and postsynaptic differentiation. It also controls the trafficking and function of several membrane proteins critical to synaptic transmission and plasticity. Very recently sumoylation has been associated with the development of neurological disorders including intellectual disability and autism.
DOES SUMOYLATION CONTROL PCDH10 FUNCTION AND DYSFUNTION?
Protocadherin-10 (Pcdh10) is a cell adhesion transmembrane protein associated with the development of autism in humans. In neurons Protocadherin-10 is involved in synapse elimination, which is a key mechanism by which neurons eliminate synaptic connection in order to increase the efficiency of neuronal transmissions and is crucial to establish a proper neuronal network. Altered synaptic elimination is a common feature in different forms of mental disorders including autism.
The project SUMO_PCDH10 aims at unraveling the role of sumoylation in controlling PCDH10 function and dysfunction in neurons.
