Naslov
The F-BAR Protein PACSIN2 Regulates Platelet Intracellular Membrane Architecture and in Vivo Hemostatic Functions

Autori
Terese Jönsson, Fred G Pluthero, Antonija Jurak Begonja, Jan Kormann, Mélanie Demers, Denisa D Wagner, Markus Plomann, John H Hartwig, Walter H Kahr and Hervé Falet

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

Skup
ASH 2014

Mjesto i datum
San Francisco (CA), Sjedinjene Američke Države, 06.12.2017. - 09.12.2017

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
PACSIN2, filamin A, platelets, megakaryocytes

Sažetak
Proteins of the Bin-amphiphysin-Rvs (BAR) and Fes-CIP4 homology BAR (F-BAR) families bind and deform membranes, promoting in cells tubular invaginations reminiscent of the platelet open canalicular system (OCS) and megakaryocyte (MK) demarcation membrane system (DMS). Here we investigated the role of the F-BAR protein PACSIN2 in platelets and MKs. Spinning disk laser fluorescence confocal microscopy showed that PACSIN2 co-localized with the von Willebrand factor receptor subunit GPIbα at the openings of the OCS in platelets. Endogenous and over-expressed PACSIN2 associated with anastomosing tubular structures reminiscent of the pre-DMS in mouse bone marrow MKs. Pacsin2- null mice had mild thrombocytopenia and polycythemia, MK hyperplasia and splenomegaly. Pacsin2-null mice had a bleeding disorder, as evidenced by significantly prolonged tail bleeding and delayed in vivo thrombus formation following FeCl3 vascular injury, which was normalized by injection of WT platelets. However, Pacsin2-null platelets expressed P- selectin and activated the integrin αIIbβ3 normally in response to stimulation with thrombin and the GPVI-specific collagen-related peptide. In contrast, Pacsin2-null platelets had abnormal flattened morphology, with more and narrower OCS channels on their surface, compared to WT platelets. Together, the data indicate that the F-BAR protein PACSIN2 orchestrates the intracellular membrane architecture of platelets, thereby regulating their in vivo hemostatic functions.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA