Record #241306 - GSI Repository

CellCellEM

Communications at the Synapse - a Near Atomic Resolution View into Cell-Cell Communication in the CNS

Grant period	2020-11-01 - 2025-10-31
Funding body	European Union
Call number	ERC-2020-STG
Grant number	949364
Identifier	G:(EU-Grant)949364

Note: Synapses are intercellular junctions specialized for coordinated cell-cell communication throughout the nervous system. They are organized by cell-adhesion molecules (CAMs) that bi-directionally orchestrate neuronal communication. Latrophilins (LPHNs) are a unique sub-family of CAMs that play critical roles in structuring the synaptic architecture through multifaceted interactions with a large variety of synaptic partners. Mutations in LPHN have been associated with neurodevelopmental and neuropsychiatric disorders. Despite their gravity, the mechanism governing LPHN synaptic activities remain elusive. To further our understanding of LPHN-mediated cell-cell communication, we suggest to characterize these receptors’ interactions with their intracellular and extracellular partners. For this purpose, we propose to adopt a hybrid approach driven primarily by cryo-EM, a state-of-the-art technique capable of dissecting the molecular mechanisms of super-molecular assemblies at extremely high spatial resolutions, which is our group’s main field of expertise. The cryo-EM studies will be complemented by cryo electron tomography (cryo-ET), fluorescence microscopy and biochemical approaches. Our specific aims are: Aim 1: Dissect the molecular mechanisms of LPHN activation by combining cryo-EM with biochemical methodologies. Aim 2: Characterize the LPHN interactome through cryo-EM and fluorescence microscopy. Aim 3: Resolve the architecture of the LPHN interactome at a close-to-native environment through cryo-ET. Our experimental strategy will generate a quantitative, near-atomic resolution view of LPHNs and the mechanism by which they interact with their synaptic partners and instigate trans-synaptic signal transduction. These data will be vital for understanding LPHN-mediated cell-cell communication as well as the mechanisms governing trans-synaptic interactions and could potentially highlight novel approaches to treat neurodevelopmental and neuropsychiatric disorders.

Recent Publications

There are no publications

Record created 2021-10-10, last modified 2023-02-08

Similar records

Add to personal basket
Export as Author List with IDs BibTeX (UTF-8), EndNote XML, EndNote Text, RIS, MARC, Print MARC, MARCXML, DC,
Request correction
Submit fulltext

GSI Homepage \| GSI Library \| English Deutsch \| guest :: login GSI Repository
Search	Submit	Personalize Your alerts Your baskets Your searches	Help