Peptides and Proteins
Jagtvej 162, 2100 København Ø
The human brain consists of a trillion neurons, which are essential for neural circuits and hence our perception, emotion and behavior. Neurons communicate via specialized junctions called synapses, and balanced synaptic transmission is essential for healthy brain function, where synapses dictate signal processing. Thus, malfunctioning synaptic transmission can lead to neurodevelopmental and neurological disorders, often triggered by genetic factors. In the excitatory glutamatergic synapse, proteins found beneath the plasma membrane in a protein-rich sub-compartment known as the post-synaptic density (PSD) are important for synaptic transmission and implicated in neurological disorders like intellectual disability, autisms spectrum disorder, and schizophrenia. The PSD is composed of densely packed assemblies of proteins, organized by protein-protein interactions (PPIs). One of the key scaffolding proteins of the PSD, is PSD-95, organizing signaling complexes primarily through its three PDZ domains. PSD-95 is heavily regulated by phosphorylation, where multiple sites have been identified using mass spectrometry and previously been introduced in recombinant proteins using semi-synthesis. My work has focused on genetically introducing site-specific phosphorylations in single, tandem and full-length PSD-95 using amber codon suppression and assessing the effect of phosphorylation on the interaction with known interaction partners, thereby identifying sites of disease importance, which can further unravel the regulation of PSD-95 in synaptic transmission and dynamics.