The intracellular and plasma membrane pools of phosphatidylinositol-4-monophosphate control megakaryocyte maturation and proplatelet formation.

Background: Megakaryocytes (MKs) develop from hematopoietic stem cells after stimulation by the cytokine thrombopoietin. During megakaryopoiesis, MKs enlarge, undergo the process of endomitosis, and develop intracellular membranes (demarcation membrane system, DMS). During DMS formation, there is active transport of proteins, lipids, and membranes from the Golgi apparatus to the DMS.

Photodynamic Inhibition of Herpes Simplex Virus 1 Infection by Tricationic Amphiphilic Porphyrin with a Long Alkyl Chain.

Photodynamic therapy (PDT) is broadly used to treat different tumors, and it is a rapidly developing approach to inactivating or inhibiting the replication of fungi, bacteria, and viruses. Herpes simplex virus 1 (HSV-1) is an important human pathogen and a frequently used model to study the effects of PDT on enveloped viruses. Although many photosensitizers (PSs) have been tested for their antiviral properties, analyses are usually limited to assessing the reduction in viral yield, and thus the molecular mechanisms of photodynamic inactivation (PDI) remain poorly understood.

Developmental differences of cultured murine bone marrow- and fetal liver-derived megakaryocytes.

Multiple lines of evidence support differences in the megakaryopoiesis during development. Murine models to study megakaryopoiesis employ cultured megakaryocytes MKs derived from adult bone marrow (BM) or fetal livers (FL) of mouse embryos. Mouse models allow to study the molecular basis for cellular changes utilizing conditional or knock-out models and permit further genetic or pharmacological manipulations.

Early Endosomal GTPase Rab5 (Ras-Related Protein in Brain 5) Regulates GPIbβ (Glycoprotein Ib Subunit β) Trafficking and Platelet Production In Vitro.

Objective: Maturation of megakaryocytes culminates with extensive membrane rearrangements necessary for proplatelet formation. Mechanisms required for proplatelet extension and origin of membranes are still poorly understood. GTPase Rab5 (Ras-related protein in brain 5) regulates endocytic uptake and homotypic fusion of early endosomes and regulates phosphatidylinositol 3-monophosphate production important for binding of effector proteins during early-to-late endosomal/lysosomal maturation.

Vps34 derived phosphatidylinositol 3-monophosphate modulates megakaryocyte maturation and proplatelet production through late endosomes/lysosomes.

Background: Development of platelet precursor cells, megakaryocytes (MKs), implies an increase in their size; formation of the elaborate demarcation membrane system (DMS); and extension of branched cytoplasmic structures, proplatelets, that will release platelets. The membrane source(s) for MK expansion and proplatelet formation have remained elusive.

Objective: We hypothesized that traffic of membranes regulated by phosphatidylinositol 3-monophosphate (PI3P) contributes to MK maturation and proplatelet formation.