Splicing-Dependent Regulation of Oligomerization of SynGAP1
Meem, Manila (2025-06-27)
Splicing-Dependent Regulation of Oligomerization of SynGAP1
Meem, Manila
(27.06.2025)
Julkaisu on tekijänoikeussäännösten alainen. Teosta voi lukea ja tulostaa henkilökohtaista käyttöä varten. Käyttö kaupallisiin tarkoituksiin on kielletty.
suljettu
Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2025070377325
https://urn.fi/URN:NBN:fi-fe2025070377325
Tiivistelmä
Synaptic GTPase-activating protein 1 (SynGAP1) is enriched in the dendritic spines of excitatory neurons. It plays a crucial role in synaptic plasticity and neuronal connectivity. SynGAP1 forms complexes with PSD-95 (postsynaptic density protein 95) and NMDA (N-methyl-D-aspartate) receptors, contributing to calcium-dependent signaling cascades. Dysregulation or mutations in the SynGAP1 gene are associated with epilepsy, autism spectrum disorders, and other neurodevelopmental disorders (NDDs). The C-terminal region of SynGAP1 includes a predicted coiled-coil domain abundant with hydrophobic residues which are mainly responsible for forming parallel and asymmetric trimers in solution. Splicing-dependent insertion of specific amino acids valine and lysine (VK) in the 5' extension of exon 17 may cause structural changes in the coiled-coil domain, affecting hydrophobic interactions that influence protein stability and function. The aim of the thesis was to study whether the presence of VK insert effect the oligomerization.
The fluorescence-based assays provided an estimate of how protein interaction works using the BRET (Bioluminescence Resonance Energy Transfer) assay between donor and acceptor in close distance through dipole-dipole coupling.
From the experiments, SynGAP1 plasmid with the combinations of donor with VK (+VK) and acceptor without VK (-VK) show higher BRET signals than combinations with donor and acceptor both with VK (+VK), suggesting stronger or more stable interactions. This indicates the influence of VK insert in the structure dynamics of the coiled-coil domain.
The fluorescence-based assays provided an estimate of how protein interaction works using the BRET (Bioluminescence Resonance Energy Transfer) assay between donor and acceptor in close distance through dipole-dipole coupling.
From the experiments, SynGAP1 plasmid with the combinations of donor with VK (+VK) and acceptor without VK (-VK) show higher BRET signals than combinations with donor and acceptor both with VK (+VK), suggesting stronger or more stable interactions. This indicates the influence of VK insert in the structure dynamics of the coiled-coil domain.