PXD064632-1

PXD064632 is an original dataset announced via ProteomeXchange.

Title	Plasma Membrane Remodelling in GM2 Gangliosidoses Drives Synaptic Dysfunction
Description	Glycosphingolipids (GSL) are important bioactive membrane components. GSLs containing sialic acids, known as gangliosides, are highly abundant in the brain and diseases of ganglioside metabolism cause severe early-onset neurodegeneration. The ganglioside GM2 is processed by β-hexosaminidaseA and when non-functional GM2 accumulates causing Tay-Sachs and Sandhoff diseases. We have developed i3Neuron-based disease models demonstrating storage of GM2 and severe endolysosomal dysfunction. Additionally, the plasma membrane (PM) is significantly altered in its lipid and protein composition. These changes are driven in part by lysosomal exocytosis causing inappropriate accumulation of lysosomal proteins on the cell surface. There are also significant changes in synaptic protein abundances with direct functional impact on neuronal activity. Lysosomal proteins are also enriched at the PM in GM1 gangliosidosis supporting that lysosomal exocytosis is a conserved mechanism of PM proteome change in these diseases. This work provides mechanistic insights into neuronal dysfunction in gangliosidoses highlighting that these are severe PM disorders with implications for other lysosomal and neurodegenerative diseases.
HostingRepository	PRIDE
AnnounceDate	2025-06-24
AnnouncementXML	Submission_2025-06-24_02:33:42.019.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alex Nicholson
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-04 07:42:44	ID requested
⏵ 1	2025-06-24 02:33:42	announced

10.1371/JOURNAL.PBIO.3003265;

submitter keyword: Quantitative proteomics, TMT, gangliosidosis, neurodegeneration

Janet Elwyn Deane
contact affiliation	Cambridge Institute for Medical Research, University of Cambridge
contact email	JED55@cam.ac.uk
lab head
Alex Nicholson
contact affiliation	CIMR
contact email	asn33@cam.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD064632
     1. Label: PRIDE project
     2. Name: Plasma Membrane Remodelling in GM2 Gangliosidoses Drives Synaptic Dysfunction