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Human erythrocytes were loaded with myo-[ 3 H]-inositol in the presence or absence of cytidine trisphosphate to investigate the synthesis of membrane phosphoinositides in the intact red cell. The addition of cytidylic nucleotides to the loading mixture yielded a four-fold increase in the [ 3 H]-labeling of the membranes. The [ 3 H]-labeling of phosphatidylinositol, phosphatidylinositol...
Botulinum neurotoxins (BoNTs) are the most toxic proteins known for humans and animals with an extremely low LD 50 of ∼1 ng/kg. BoNTs generally require a protein and a ganglioside on the cell membrane surface for binding, which is known as a “dual receptor” mechanism for host intoxication. Recent studies have suggested that in addition to gangliosides, other membrane lipids such as phosphoinositides...
Phosphoinositide-specific phospholipase C (PI-PLC) cleaves, in a Ca 2+ -dependent manner, phosphatidylinositol-4,5-bisphosphate (PI-4,5-P 2 ) into diacylglycerol (DAG) and inositol triphosphate (IP 3 ). PI-PLCs are multidomain proteins that are structurally related to the PI-PLCζs, the simplest animal PI-PLCs. Like these animal counterparts, they are only composed of EF-hand,...
Phosphoinositide 3-kinases (PI3Ks) are a family of lipid kinases that phosphorylates the 3′OH of the inositol ring of phosphoinositides (PIs). They are responsible for coordinating a diverse range of cellular functions. Class IA PI3K is a heterodimeric protein composed of a regulatory p85 and a catalytic p110 subunit. In this study, we conditionally deleted the p110α-subunit of PI3K in cone photoreceptor...
By interacting specifically with proteins, phosphoinositides organize the spatiotemporal formation of protein complexes involved in the control of intracellular signaling, vesicular trafficking and cytoskeleton dynamics. A set of specific kinases and phosphatases ensures the production, degradation and inter-conversion of phosphoinositides to achieve a high level of precision in the regulation of...
Phospholipases play a key role in the metabolism of phospholipids and in cell signaling. They are also a very useful tool to explore phospholipid structure and metabolism as well as membrane organization. They are at the center of this review, covering a period starting in 1971 and focused on a number of subjects in which my colleagues and I have been involved. Those include determination of phospholipid...
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