Periodic Reporting for period 1 - SUMO-PCDH10 (Physiological consequences of Protocadherin-10 sumoylation on neuronal function.)
Okres sprawozdawczy: 2019-06-01 do 2021-05-31
Thus, the overall goal of my research project is to unveil the physiopathological consequences of Pcdh10 sumoylation in neurons.
Conversely, neither the number and architecture of inhibitory synapses nor the frequency and amplitude of miniature inhibitory postsynaptic currents (mIPSCs) were impaired in Pcdh10 silenced neurons, indicating that Pcdh10 is essential in the physiology of excitatory but not inhibitory synapses.
Interestingly, rescue experiments demonstrated that reintroducing the non sumoylatable form of Pcdh10 failed in rescuing the dendritic spine density in Pcdh10-silenced neurons. Conversely, the WT and K831R forms of Pcdh10 properly restored the mEPSCs frequency defects induced by Pcdh10 knockdown.
Altogether, our results demonstrate that sumoylation is an essential mechanism controlling the Pcdh10 physiological role in neurons and that perturbing such process compromises excitatory synapse formation.
The regulation of synaptic strength, spine architecture and density are key processes for the control of neuronal functions and are altered in several forms of autism. Thus, my results, by providing key information on the physiological role of Pcdh10 sumoylation, highlight sumoylation as a novel regulatory mechanism in excitatory synapse maturation and function. This pioneers a novel and stimulating topic in the neuroscience field aiming at uncovering the role of sumoylation on the etiology of mental disorders.