Naslov
OCRL phosphatase controls actin reorganization in human and mouse platelets spread on different matrices

Autori
Bura, Ana ; Stainano Leopoldo ; Morra, Valentina ; De Matteis, Antonietta Maria ; Jurak Begonja, Antonija

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Book of abstracts / - , 2020, 76-76

Skup
EMBL studentski kongres: The Roaring 20s: A New Decade for Life Sciences

Mjesto i datum
Online, 27.-28. 11. 2020

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
OCRL, PI(4, 5)P2, platelets, Lowe syndrome

Sažetak
Phosphoinositides (PIs) are phosphorylated membrane lipids that control the function of secretory organelles, act as signal transducers and have a role in actin reorganization, cell growth, and proliferation. One of seven different PIs is phosphatidylinositol-4, 5- bisphosphate [PI(4, 5)P2] which is found at the plasma membrane (PM) and is important for the regulation of actin reorganization. Inositol polyphosphate 5-phosphatase OCRL-1, also known as Lowe oculocerebrorenal syndrome protein, is an enzyme that dephosphorylates PI(4, 5)P2 and is involved in actin polymerization. Mutations in OCRL cause Lowe syndrome which is characterized with congenital cataracts, central hypotonia and renal proximal tubular dysfunction. Increased tendency for bleedings and aberrant platelet (PLT) activation was shown in some patients with Lowe syndrome (Lasne et al., 2010). PLTs have a major role in hemostasis by detecting vessel wall injury. They recognize extracellular matrix proteins, become activated and aggregate to prevent bleeding. We hypothesize that the loss of OCRL function and the subsequent increase of PI(4, 5)P2 leads to the changes in actin dynamics resulting in PLT dysfunction. Here, we show that human and mouse PLTs with pharmacologically inhibited OCRL fail to fully spread on different matrices (glass, fibrinogen and collagen). When spread on fibrinogen, inhibitor treated human PLTs form less lamellipodia with extensive filopodia while containing more actin rich structures, called nodules, compared to the untreated PLTs. These actin nodules colocalize with proteins engaged in actin dynamics such as vinculin, ARP2/3 complex and SNX9, as well as with phosphotyrosine suggesting they are sites of ongoing signaling. In line with pharmacological data, platelets isolated from mice deficient in OCRL also fail to fully activate and spread on fibrinogen and collagen. Our data suggest that OCRL might control actin cytoskeleton rearrangements during platelet activation and thus their proper function. Further studies are underway to clarify involved signaling pathways.

Izvorni jezik
Engleski

Znanstvena područja
Biotehnologija u biomedicini (prirodno područje, biomedicina i zdravstvo, biotehničko područje)

POVEZANOST RADA