PXD034588

PXD034588 is an original dataset announced via ProteomeXchange.

Title	Splenectomy of patients with hereditary spherocytosis improves erythrocyte functionality in a septin-dependent manner
Description	Splenectomy improves clinical parameters of patients with hereditary spherocytosis but its potential benefit to red blood cell (RBC) morphology and deformability and the mechanism behind remain unknown. We here compared 7 non-splenectomized and 12 splenectomized patients with mutations in the β-spectrin (SPTB) or the ankyrin (ANK1) gene. We showed that hematological parameters, spherocyte abundance, osmotic fragility, intracellular calcium and extracellular vesicle release were largely restored by splenectomy, but cryohemolysis was not. To elucidate the only partial improvement of RBC morphology and deformability by splenectomy, we performed a quantative proteomic analysis and cytoskeleton characterization. Patients exhibited decreased ankyrin and/or β-spectrin contents but the extent of RBC alteration only slightly and negatively correlated with the ankyrin and not with β-spectrin content nor membrane association. In contrast, patients exhibited increased abundance of septins, small GTP-binding cytoskeletal proteins involved in cytokinesis. Among the four septins detected, septins-2,7 and 8 but not 11 were less abundant upon splenectomy and correlated with the disease severity. The septin increase was accompanied by exacerbated oxidative stress especially in the non splenectomized patients. Except cryohemolysis, all the RBC morphology and deformability alterations and oxidative stress correlated with septin content. Impairments can result from RBC maturation defects since endoplasmic reticulum remnants were found in RBCs from non-splenectomized patients and lysosomal and mitochondrial remnants in splenectomised patients. The correlation between septin abundance and disease severity opens the way towards using septins as disease biomarkers. Moreover, the absence of restoration of septin-independent cryohemolysis by splenectomy could question its systematic recommendation
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:56:17.712.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD034588
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Didier Vertommen
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	2022-06-16 03:09:37	ID requested
1	2023-02-13 01:06:55	announced
⏵ 2	2023-11-14 08:56:18	announced	2023-11-14: Updated project metadata.

10.6019/PXD034588;

submitter keyword: calcium,red blood cell fragility, oxidative stress, extracellular vesicle release, RBC maturation, spectrin network, ankyrin

Donatienne Tyteca
contact affiliation	CELL Unit & PICT Imaging Platform, de Duve Institute, UCLouvain, UCL B1.75.05, Avenue Hippocrate, 75, B-1200 Brussels, Belgium. Phone: +32-2-764.75.91; Fax: +32-2-764.75.43
contact email	donatienne.tyteca@uclouvain.be
lab head
Didier Vertommen
contact affiliation	UCL - de Duve Institute, Brussels Belgium
contact email	didier.vertommen@uclouvain.be
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD034588
     1. Label: PRIDE project
     2. Name: Splenectomy of patients with hereditary spherocytosis improves erythrocyte functionality in a septin-dependent manner