PXD016851

PXD016851 is an original dataset announced via ProteomeXchange.

Title	Study of APOL1-containing complexes in podocytes
Description	The C-terminal variants G1 and G2 of apolipoprotein L1 (APOL1) confer human resistance to the sleeping sickness parasite Trypanosoma rhodesiense, but also increase the risk of developing kidney disease. APOL1 and APOL3 are death-promoting proteins associated with endoplasmic reticulum and Golgi membranes. We report that in podocytes, either expression of APOL1 devoid of C-terminal helix (APOL1) or deletion of APOL3 (APOL3 KO) induce actomyosin reorganization linked to inhibition of phosphatidylinositol-4-phosphate (PI(4)P) synthesis by the Golgi PI(4)-kinase IIIB (PI4KB). Both APOL1 and APOL3 form K+ channels, but only APOL3 exhibited Ca2+-dependent binding to neuronal calcium sensor-1 (NCS-1), promoting NCS-1/PI4KB interaction that strongly activates PI(4)P synthesis. APOL1 C-terminal deletion or mutations increased APOL1 binding to APOL3, affecting APOL3 interaction with NCS-1. Since podocytes of G1 and G2 patients exhibited an APOL1/APOL3KO-like phenotype, APOL1 C-terminal variants may induce kidney disease by preventing APOL3 from activating PI4KB, resulting in actomyosin reorganization of podocytes.
HostingRepository	PRIDE
AnnounceDate	2020-03-19
AnnouncementXML	Submission_2020-06-12_02:59:38.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD016851
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Marc Dieu
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	Ammonia-loss; 2-pyrrolidone-5-carboxylic acid (Gln); Dehydrated; Oxidation; Acetyl; Carbamidomethyl; monohydroxylated residue; iodoacetamide derivatized residue; Gln->pyro-Glu
Instrument	maXis

Revision	Datetime	Status	ChangeLog Entry
0	2019-12-19 07:03:13	ID requested
1	2020-03-19 06:54:31	announced
⏵ 2	2020-06-12 02:59:39	announced	2020-06-12: Updated publication reference for PubMed record(s): 32187552.

Uzureau S, Lecordier L, Uzureau P, Hennig D, Graversen JH, Hombl, é F, Mfutu PE, Oliveira Arcolino F, Ramos AR, La Rovere RM, Luyten T, Vermeersch M, Tebabi P, Dieu M, Cuypers B, Deborggraeve S, Rabant M, Legendre C, Moestrup SK, Levtchenko E, Bultynck G, Erneux C, P, é, rez-Morga D, Pays E, APOL1 C-Terminal Variants May Trigger Kidney Disease through Interference with APOL3 Control of Actomyosin. Cell Rep, 30(11):3821-3836.e13(2020) [pubmed]

curator keyword: Biomedical

submitter keyword: APOL1, Kidney disease, podocytes

Etienne PAYS
contact affiliation	Laboratory of Molecular Parasitology, IBMM, Université Libre de Bruxelles, B-6041 Gosselies, Belgium
contact email	etiennepays@gmail.com
lab head
Marc Dieu
contact affiliation	University of Namur - MaSUN
contact email	marc.dieu@unamur.be
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD016851
     1. Label: PRIDE project
     2. Name: Study of APOL1-containing complexes in podocytes