PXD054623-1

PXD054623 is an original dataset announced via ProteomeXchange.

Title	LRRTM2 controls presynapse nano-organization and AMPA receptor sub-positioning through Neurexin-binding interface
Description	Synapses are organized into nanocolumns that control neurotransmission efficacy through precise alignment of postsynaptic AMPARs and presynaptic release sites. How these are trans-synaptically arranged remains elusive, despite evidence involving adhesion proteins. Highly enriched and confined at synapses, Leucine-Rich Repeat Transmembrane protein LRRTM2, is ideally poised to play this role by interacting with presynaptic Neurexins. Recent evidence show that LRRTM2 interacts with Neurexins through the C-terminal cap of LRRTM2 extracellular domain, but the role of this binding interface containing E348 has not been explored in synapse formation and function. Here, we developed a conditional knock-out mouse model (cKO) to address these questions and iden-tify LRRTM2 as a critical regulator of synapse nano-organization. We show that LRRTM2 cKO specifically impairs excitatory synapse formation and function. Surface expression, synaptic clustering, and membrane diffusion are tightly controlled by different motifs in LRRTM2 C-terminal domain, while the N-terminal domain controls pre-synapse nano-organization, AMPARs sub-positioning and stabilization, through the recently identified Neurexin-binding interface. Thus, LRRTM2 appears as a central organizer of synapse nanostructure through interaction with presynaptic Neurexins.
HostingRepository	PRIDE
AnnounceDate	2024-09-18
AnnouncementXML	Submission_2024-09-18_06:16:28.663.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Stephane Claverol
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-08-06 00:17:45	ID requested
⏵ 1	2024-09-18 06:16:29	announced
2	2024-10-22 06:59:03	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: Synapse, LRRTM

Stephane Claverol
contact affiliation	Univ. Bordeaux, Bordeaux Proteome, Bordeaux, France
contact email	stephane.claverol@u-bordeaux.fr
lab head
Stephane Claverol
contact affiliation	Plateforme Proteome
contact email	stephane.claverol@u-bordeaux.fr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD054623
     1. Label: PRIDE project
     2. Name: LRRTM2 controls presynapse nano-organization and AMPA receptor sub-positioning through Neurexin-binding interface