Impaired microtubule dynamics contribute to microthrombocytopenia in RhoB-deficient mice.

Megakaryocytes are large cells in the bone marrow that give rise to blood platelets. Platelet biogenesis involves megakaryocyte maturation, the localization of the mature cells in close proximity to bone marrow sinusoids, and the formation of protrusions, which are elongated and shed within the circulation. Rho GTPases play important roles in platelet biogenesis and function.

Generation of a humanized FXII knock-in mouse-A powerful model system to test novel anti-thrombotic agents.

Background: Effective inhibition of thrombosis without generating bleeding risks is a major challenge in medicine. Accumulating evidence suggests that this can be achieved by inhibition of coagulation factor XII (FXII), as either its knock-out or inhibition in animal models efficiently reduced thrombosis without affecting normal hemostasis. Based on these findings, highly specific inhibitors for human FXII(a) are under development.

Molecular docking between human TMPRSS2 and SARS-CoV-2 spike protein: conformation and intermolecular interactions.

Entry of SARS-CoV-2, etiological agent of COVID-19, in the host cell is driven by the interaction of its spike protein with human ACE2 receptor and a serine protease, TMPRSS2. Although complex between SARS-CoV-2 spike protein and ACE2 has been structurally resolved, the molecular details of the SARS-CoV-2 and TMPRSS2 complex are still elusive. TMPRSS2 is responsible for priming of the viral spike protein that entails cleavage of the spike protein at two potential sites, Arg685/Ser686 and Arg815/Ser816.

Dataset for homologous proteins in for SARS-CoV-2/human interactome.

Animal modelling for infectious diseases is critical to understand the biology of the pathogens including viruses and to develop therapeutic strategies against it. Herein, we present the sequence homology and expression data analysis of proteins found in that are orthologous to human proteins, reported as components of SARS-CoV-2/Human interactome. The dataset enlists sequence homology, query coverage, domain conservation, OrthoMCL and Ensembl Genome Browser support of 326 proteins in that are potentially orthologous to 417 human proteins reported for their direct physical interactions with 28 proteins encoded by SARS-CoV-2 genome.

Structural variations in human ACE2 may influence its binding with SARS-CoV-2 spike protein.

The recent pandemic of COVID-19, caused by SARS-CoV-2, is unarguably the most fearsome compared with the earlier outbreaks caused by other coronaviruses, SARS-CoV and MERS-CoV. Human ACE2 is now established as a receptor for the SARS-CoV-2 spike protein. Where variations in the viral spike protein, in turn, lead to the cross-species transmission of the virus, genetic variations in the host receptor ACE2 may also contribute to the susceptibility and/or resistance against the viral infection.

Critical redundant functions of the adapters Grb2 and Gads in platelet (hem)ITAM signaling in mice.

Platelets are essential for normal hemostasis; however, pathological conditions can also trigger unwanted platelet activation precipitating thrombosis and ischemic damage of vital organs such as the heart or brain. (GP)VI- and (CLEC-2)-mediated (hem) (ITAM) signaling represents a major pathway for platelet activation. The two members of the (Grb2) family of adapter proteins expressed in platelets - Grb2 and (Gads) - are part of the hem(ITAM) signaling cascade by forming an adapter protein complex with (LAT).

A Cdc42/RhoA regulatory circuit downstream of glycoprotein Ib guides transendothelial platelet biogenesis.

Blood platelets are produced by large bone marrow (BM) precursor cells, megakaryocytes (MKs), which extend cytoplasmic protrusions (proplatelets) into BM sinusoids. The molecular cues that control MK polarization towards sinusoids and limit transendothelial crossing to proplatelets remain unknown. Here, we show that the small GTPases Cdc42 and RhoA act as a regulatory circuit downstream of the MK-specific mechanoreceptor GPIb to coordinate polarized transendothelial platelet biogenesis.

TMEM16F-Mediated Platelet Membrane Phospholipid Scrambling Is Critical for Hemostasis and Thrombosis but not Thromboinflammation in Mice-Brief Report.

Objective: It is known that both platelets and coagulation strongly influence infarct progression after ischemic stroke, but the mechanisms and their interplay are unknown. Our aim was to assess the contribution of the procoagulant platelet surface, and thus platelet-driven thrombin generation, to the progression of thromboinflammation in the ischemic brain.

Approach And Results: We present the characterization of a novel platelet and megakaryocyte-specific TMEM16F (anoctamin 6) knockout mouse.