No abstract

Membrane biology seeks to understand how lipids and proteins within bilayers assemble into large structures such as organelles and the plasma membranes. Historically, lipids were thought to merely provide structural support for bilayer formation and membrane protein function. Research has now revealed that phospholipid metabolism regulates nearly all cellular processes. Sophisticated techniques helped identify >10,000 lipid species suggesting that lipids support many biological processes. Here, we highlight the synthesis of the most abundant glycerophospholipid classes and their distribution in organelles. We review vesicular and nonvesicular transport pathways shuttling lipids between organelles and discuss lipid regulators of membrane trafficking and second messengers in eukaryotic cells.

The outbreak of the novel coronavirus infectious disease 2019 (COVID-19) caused by the SARS-CoV-2 virus has rapidly spread around the world. Increasing evidence has suggested that patients with COVID-19 may present neurological symptoms, and cerebrovascular diseases are one of the most frequent comorbidities. The markedly elevated D-dimer levels in patients with acute ischemic stroke suggests that SARS-CoV-2 infection may induce an inflammatory response and trigger a hypercoagulation state, thus leading to acute ischemic stroke. Cardioembolism and atherosclerosis in patients with COVID-19 infection may also increase the risk of ischemic stroke. The reduction of the angiotensin-converting enzyme II (ACE2) caused by SARS-CoV-2 binding to the ACE2 receptor can lead to abnormally elevated blood pressure and increase the risk of hemorrhagic stroke. Additionally, the cytokine storm induced by the immune response against the viral infection increases the risk of acute stroke. The management for COVID-19 patients with stroke is not only based on the traditional guidelines, but also based on the experience and new instructions from healthcare workers worldwide who are combatting COVID-19.

Edited by Dennis R. VoelkerCaveolae are bulb-shaped nanodomains of the plasma membrane that are enriched in cholesterol and sphingolipids. They have many physiological functions, including endocytic transport, mechanosensing, and regulation of membrane and lipid transport. Caveola formation relies on integral membrane proteins termed caveolins (Cavs) and the cavin family of peripheral proteins. Both protein families bind anionic phospholipids, but the precise roles of these lipids are unknown. Here, we studied the effects of phosphatidylserine (PtdSer), phosphatidylinositol 4-phosphate (PtdIns4P), and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P 2 ) on caveolar formation and dynamics. Using live-cell, single-particle tracking of GFP-labeled Cav1 and ultrastructural analyses, we compared the effect of PtdSer disruption or phosphoinositide depletion with caveola disassembly caused by cavin1 loss. We found that PtdSer plays a crucial role in both caveola formation and stability. Sequestration or depletion of PtdSer decreased the number of detectable Cav1-GFP puncta and the number of caveolae visualized by electron microscopy. Under PtdSer-limiting conditions, the co-localization of Cav1 and cavin1 was diminished, and cavin1 degradation was increased. Using rapamycin-recruitable phosphatases, we also found that the acute depletion of PtdIns4P and PtdIns (4,5)P 2 has minimal impact on caveola assembly but results in decreased lateral confinement. Finally, we show in a model of phospholipid scrambling, a feature of apoptotic cells, that caveola stability is acutely affected by the scrambling. We conclude that the predominant plasmalemmal anionic lipid PtdSer is essential for proper Cav clustering, caveola formation, and caveola dynamics and that membrane scrambling can perturb caveolar stability.