ABSTRACT
Polyphosphoinositides (PPIns) are a family of seven lipid messengers that regulate a vast array of signalling pathways to control cell proliferation, migration, survival and differentiation. PPIns are differentially present in various sub-cellular compartments and, through the recruitment and regulation of specific proteins, are key regulators of compartment identity and function. Phosphoinositides and the enzymes that synthesise and degrade them are also present in the nuclear membrane and in nuclear membraneless compartments such as nuclear speckles. Here we discuss how PPIns in the nucleus are modulated in response to external cues and how they function to control downstream signalling. Finally we suggest a role for nuclear PPIns in liquid phase separations that are involved in the formation of membraneless compartments within the nucleus.
Subject(s)
Cell Nucleus/metabolism , Lipid Metabolism , Phosphatidylinositols/metabolism , Animals , Chemical Phenomena , Computational Biology , Humans , Intranuclear Space/metabolism , Metabolic Networks and Pathways , Nuclear Envelope/metabolism , Phosphatidylinositol 4,5-Diphosphate/chemistry , Phosphatidylinositol 4,5-Diphosphate/metabolism , Phosphatidylinositols/chemistry , Signal TransductionABSTRACT
Several studies have demonstrated the existence of an autonomous intranuclear phospho-inositide cycle that involves the activation of nuclear PI-PLC and the generation of diacylglycerol (DG) within the nucleus. Although several distinct isozymes of PI-PLC have been detected in the nucleus, the isoform that has been most consistently highlighted as being nuclear is PI-PLC-beta1. Nuclear PI-PLC-beta1 has been linked with either cell proliferation or differentiation. Remarkably, the activation mechanism of nuclear PI-PLC-beta1 has been shown to be different from its plasma membrane counterpart, being dependent on phosphorylation effected by p44/42 mitogen activated protein (MAP) kinase. In this review, we report the most up-dated findings about nuclear PI-PLC-beta1, such as the localization in nuclear speckles, the activity changes during the cell cycle phases, and the possible involvement in the progression of myelodisplastic syndrome to acute myeloid leukemia.
Subject(s)
Cell Nucleus/enzymology , Isoenzymes/physiology , Lipids/physiology , Signal Transduction/physiology , Type C Phospholipases/physiology , Amino Acid Sequence , Animals , Cell Cycle/physiology , Cell Nucleus/chemistry , Humans , Isoenzymes/chemistry , Isoenzymes/genetics , Molecular Sequence Data , Neoplasm Proteins/chemistry , Neoplasm Proteins/genetics , Neoplasm Proteins/physiology , Phospholipase C beta , Type C Phospholipases/chemistry , Type C Phospholipases/geneticsABSTRACT
The authors present a new investigation technique by means of CT of the frontal sinus drainage pathway, the frontal recess, which could be of considerable help in defining its potential role in determining a chronic or recurrent inflammatory process of this cavity. Among the main characteristics of this technique are: (1) a clear presentation of the course and conformation of the recess and its relations with surrounding structures; (2) speedy, and therefore economical, operation (12 min for a complete examination); and (3) tolerability, because this examination starts off with axial-scans, which, compared to CT coronal projections and MRI scans, are less prone to defects and do not require strained postures. This this means that all kinds of patients can be assessed, which is a basic requirement for achieving standardisation. With axial scans the authors work from paraxial reconstructions (oblique sagittal) which, in their opinion, give the best definition of the frontal recess so far recorded.
