Abstract
The dynamic re-organization of cellular membranes in response to extracellular stimuli is fundamental to the cell physiology of myeloid and lymphoid cells of the immune system. In addition to maintaining cellular homeostatic functions, remodeling of the plasmalemma and endomembranes endow leukocytes with the potential to relay extracellular signals across their biological membranes to promote rolling adhesion and diapedesis, migration into the tissue parenchyma, and to ingest foreign particles and effete cells. Phosphoinositides, signaling lipids that control the interface of biological membranes with the external environment, are pivotal to this wealth of functions. Here, we highlight the complex metabolic transitions that occur to phosphoinositides during several stages of the leukocyte lifecycle, namely diapedesis, migration, and phagocytosis. We describe classical and recently developed tools that have aided our understanding of these complex lipids. Finally, major downstream effectors of inositides are highlighted including the cytoskeleton, emphasizing the importance of these rare lipids in immunity and disease.
Highlights
Chemotaxis and phagocytosis are fundamental processes employed by myeloid cells of the immune system to protect the body from harmful invading microorganisms and maintain tissue homeostasis
We showed that tubules emerge from the PtdIns(4)P-rich clusters in the resolving phagolysosome, where ADP-ribosylation factor-like protein 8B (ARL8B) and SifAand kinesin-interacting protein/pleckstrin homology domaincontaining family M member 2 (SKIP/PLEKHM2) accumulate
The development of fluorescent biosensors of PPIns provided an unparalleled tool to investigate the role of these key lipids in leukocyte biology
Summary
Chemotaxis and phagocytosis are fundamental processes employed by myeloid cells of the immune system to protect the body from harmful invading microorganisms and maintain tissue homeostasis. Proximal tissues are flagged for recognition by the production of inflammatory mediators (Nathan, 2006) Neutrophils sense these pathogen-associated molecules and inflammatory signals through various receptors including Toll-like receptors (TLRs) and G protein-coupled receptors (GPCRs). Neutrophils undertake diapedesis to exit blood vessels and migrate toward the site of infection within the tissue parenchyma to deploy antimicrobial functions, including but not limited to phagocytosis (Mayadas et al, 2014). They generate reactive oxygen species, release antimicrobial. We describe the current tools used to study and manipulate phosphoinositides and, when possible, offer insights of their relevance to health and disease
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