PXD052081-1

PXD052081 is an original dataset announced via ProteomeXchange.

Title	Synaptic Signatures and Disease Vulnerabilities of Layer 5 Pyramidal Neurons - second data set
Description	Cortical layer 5 (L5) intratelencephalic (IT) and pyramidal tract (PT) neurons are embedded in distinct information processing pathways. The morphology, connectivity, electrophysiological properties, and role in behavior of these neurons have been extensively analyzed. However, the molecular composition of their synapses remains largely uncharacterized. Here, we dissect the protein composition of the excitatory postsynaptic compartment of L5 neurons in intact somatosensory circuits, using an optimized proximity biotinylation workflow with subsynaptic resolution. We find distinct synaptic signatures of L5 IT and PT neurons that are defined by proteins regulating synaptic organization and transmission, including cell-surface proteins (CSPs), neurotransmitter receptors and ion channels. In addition, we find a differential vulnerability to disease, with a marked enrichment of autism risk genes in the synaptic signature of L5 IT neurons compared to PT neurons. Our results align with human studies and suggest that the excitatory postsynaptic compartment of L5 IT neurons is notably susceptible in autism. Together, our analysis sheds light on the proteins that regulate synaptic organization and function of L5 neuron types and contribute to their susceptibility in disease. Our approach is versatile and can be broadly applied to other neuron types to create a protein-based, synaptic atlas of cortical circuits.
HostingRepository	PRIDE
AnnounceDate	2024-11-04
AnnouncementXML	Submission_2024-11-04_12:53:06.798.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Andrew Howden
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-05-07 09:24:00	ID requested
⏵ 1	2024-11-04 12:53:07	announced

Dataset with its publication pending

submitter keyword: neurons, synapses

Professor Joris de Wit
contact affiliation	VIB Center for Brain & Disease Research, Herestraat 49, 3000 Leuven, Belgium.
contact email	joris.dewit@kuleuven.be
lab head
Andrew Howden
contact affiliation	University of Dundee
contact email	a.howden@dundee.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD052081
     1. Label: PRIDE project
     2. Name: Synaptic Signatures and Disease Vulnerabilities of Layer 5 Pyramidal Neurons - second data set