PXD025286

PXD025286 is an original dataset announced via ProteomeXchange.

Title	Synaptic protein S-palmitoylation as a novel mechanism underlying sex-dependent differences in neuronal plasticity
Description	Although sex differences in the brain are prevalent, the knowledge about mechanisms underlying sex-related effects on normal and pathological brain functioning is rather poor. It is known that female and male brains differ in size and connectivity. Moreover, those differences are related to neuronal morphology and activity, synapse molecular organization, synaptic plasticity, and molecular signalling pathways. Among different processes assuring proper synapse function are posttranslational modifications, and among them, S-palmitoylation emerges as a crucial mechanism underlying synaptic integrity. Protein S-palmitoylation (S-PALM) refers to the covalent attachment of palmitic acid (C16:0) to cysteine residue(s) via the formation of a thioester bond. Protein S-PALM is governed by a family of PATs, also known as DHHC proteins. Here we focused on the sex-related functional importance of DHHC7 acyltransferase. Under physiological conditions, DHHC7 emerges of particular interest because it palmitoylates various synaptic proteins involved in the regulation of cellular polarity and proliferation as well as in stress and anxiety-related pathology. Moreover, DHHC7 is responsible for S-PALM of sex steroid receptors. Functionally, S-PALM of these receptors regulates their trafficking to the plasma membrane as well as their rapid responses to sex steroid hormones. Using mass spectrometry-based method PANIMoni we identified sex-dependent differences in the S-palmitoylation of synaptic proteins, potentially involved in the regulation of passive membrane properties and excitability (e.g. potassium voltage-gated channels), synaptic transmission (e.g. subunits of glutamate or kainate receptors, voltage-dependent calcium channels) as well as signalling proteins involved in structural plasticity of dendritic spines (e.g. G-proteins and Rab GTPase). Furthermore, to determine a mechanistic source for sex-dependent changes in protein S-palmitoylation we used synaptoneurosomes from DHHC-7 knock-out -/- (DHHC7 KO) female and male mice. Our data showed sex-dependent action of DHHC-7 acyltransferase. Such discovery will facilitate the development of novel and targeted treatments congruous with biological sex.
HostingRepository	PRIDE
AnnounceDate	2021-06-23
AnnouncementXML	Submission_2021-06-22_22:04:36.790.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Monika Zareba-Koziol
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2021-04-08 19:46:55	ID requested
⏵ 1	2021-06-22 22:04:37	announced

Dataset with its publication pending

submitter keyword: palmitoylation, sex-dependent,DHHC7

Jakub Włodarczyk
contact affiliation	Laboratory of Cell Biophysics Nencki Institute of Experimental Biology PAS Warsaw, Poland
contact email	j.wlodarczyk@nencki.edu.pl
lab head
Monika Zareba-Koziol
contact affiliation	Laboratory of Cell Biophysics, Nencki Institute of Experimental Biology, PAS
contact email	m.zareba-koziol@nencki.gov.pl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD025286
     1. Label: PRIDE project
     2. Name: Synaptic protein S-palmitoylation as a novel mechanism underlying sex-dependent differences in neuronal plasticity