Pregled bibliografske jedinice broj: 1220974
Oculocerebrorenal syndrome of Lowe protein controls cytoskeletal reorganisation during human platelet spreading
Oculocerebrorenal syndrome of Lowe protein controls cytoskeletal reorganisation during human platelet spreading // British Journal of Haematology, (2022), 00; 1-13 doi:10.1111/bjh.18478 (međunarodna recenzija, članak, znanstveni)
CROSBI ID: 1220974 Za ispravke kontaktirajte CROSBI podršku putem web obrasca
Naslov
Oculocerebrorenal syndrome of Lowe protein
controls cytoskeletal reorganisation during human
platelet spreading
Autori
Bura, Ana ; de Matteis, Maria Antonietta ; Bender, Markus ; Swinkels, Maurice ; Versluis, Jurjen ; Jansen, A. J. Gerard ; Jurak Begonja, Antonija
Izvornik
British Journal of Haematology (0007-1048)
(2022), 00;
1-13
Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni
Ključne riječi
actin, bleeding disorders, Lowe syndrome, microtubules, nodules, OCRL, platelet function
Sažetak
Lowe syndrome (LS) is a rare, X-linked disorder characterised by numerous symp-toms affecting the brain, the eyes, and the kidneys. It is caused by mutations in the oculocerebrorenal syndrome of Lowe (OCRL) protein, a 5-phosphatase localised in different cellular compartments that dephosphorylates phosphatidylinositol-4, 5- bisphosphate into phosphatidylinositol-4- monophosphate. Some patients with LS also have bleeding disorders, with normal to low platelet (PLT) count and impaired PLT function. However, the mechanism of PLT dysfunction in patients with LS is not completely understood. The main function of PLTs is to activate upon vessel wall injury and stop the bleeding by clot formation. PLT activation is accompanied by a shape change that is a result of massive cytoskeletal rearrangements. Here, we show that OCRL-inhibited human PLTs do not fully spread, form mostly filopodia, and accumulate actin nodules. These nodules co-localise with ARP2/3 subunit p34, vinculin, and sorting nexin 9. Furthermore, OCRL-inhibited PLTs have a retained microtubular coil with high levels of acetylated tubulin. Also, myosin light chain phosphorylation is decreased upon OCRL inhibition, without impaired degranula-tion or integrin activation. Taken together, these results suggest that OCRL contributes to cytoskeletal rearrangements during PLT activation that could explain mild bleeding problems in patients with LS.
Izvorni jezik
Engleski
Znanstvena područja
Biologija, Temeljne medicinske znanosti, Biotehnologija u biomedicini (prirodno područje, biomedicina i zdravstvo, biotehničko područje)
POVEZANOST RADA
Projekti:
Ostalo-ASH-2019 - Nucleolar control of megakaryopoiesis (NucMeg) (Jurak Begonja, Antonija, Ostalo - American Society of Hematology (ASH) Global Research Award) ( CroRIS)
HRZZ-DOK-2018-01-7426 - Projekt razvoja karijera mladih istraživača – izobrazba novih doktora znanosti (Jurak Begonja, Antonija, HRZZ ) ( CroRIS)
HRZZ-UIP-2014-09-2400 - Uloga fosfoinozitida u nastanku trombocita (MkPI) (Jurak Begonja, Antonija, HRZZ - 2014-09) ( CroRIS)
NadSve-Sveučilište u Rijeci-uniri-biomed-18-188-1343 - Identifikacija novih interakcijskih partnera Vps34 u megakariopoezi (Jurak Begonja, Antonija, NadSve - UNIRI projekti 2018) ( CroRIS)
Ustanove:
Sveučilište u Rijeci - Odjel za biotehnologiju
Citiraj ovu publikaciju:
Časopis indeksira:
- Current Contents Connect (CCC)
- Web of Science Core Collection (WoSCC)
- Science Citation Index Expanded (SCI-EXP)
- SCI-EXP, SSCI i/ili A&HCI
- Scopus
- MEDLINE