Sphingomyelin Breakdown in T Cells: Role of Membrane Compartmentalization in T Cell Signaling and Interference by a Pathogen

Abstract

Sphingolipids are major components of cellular membranes, and at steady-state level, their metabolic fluxes are tightly controlled. On challenge by external signals, they undergo rapid turnover, which substantially affects the biophysical properties of membrane lipid and protein compartments and, consequently, signaling and morphodynamics. In T cells, external cues translate into formation of membrane microdomains where proximal signaling platforms essential for metabolic reprograming and cytoskeletal reorganization are organized. This review will focus on sphingomyelinases, which mediate sphingomyelin breakdown and ensuing ceramide release that have been implicated in T-cell viability and function. Acting at the sphingomyelin pool at the extrafacial or cytosolic leaflet of cellular membranes, acid and neutral sphingomyelinases organize ceramide-enriched membrane microdomains that regulate T-cell homeostatic activity and, upon stimulation, compartmentalize receptors, membrane proximal signaling complexes, and cytoskeletal dynamics as essential for initiating T-cell motility and interaction with endothelia and antigen-presenting cells. Prominent examples to be discussed in this review include death receptor family members, integrins, CD3, and CD28 and their associated signalosomes. Progress made with regard to experimental tools has greatly aided our understanding of the role of bioactive sphingolipids in T-cell biology at a molecular level and of targets explored by a model pathogen (measles virus) to specifically interfere with their physiological activity.

Plasma Metabolome Profiling Identifies Metabolic Subtypes of Pancreatic Ductal Adenocarcinoma

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Lipid larceny: channelizing host lipids for establishing successful pathogenesis by bacteria

“…Studies on primary human nasal and murine tracheal epithelial cells showed that it triggers lipid microdomain transformation into large platforms of insoluble membranes to stimulate its internalization [ 109 ], the stimulation of CD95 and CD40 trigger membrane reorganization subjecting acid sphingomyelinase (ASM) toward the extracellular leaflet. Thus, leading to the breakdown of sphingomyelin to ceramide [ 110 , 111 ]. This is further required to reorganize these microdomains into larger signaling platforms [ 112 ].…”

Molecular Mechanisms of Lipid Metabolism Disorders in Infectious Exacerbations of Chronic Obstructive Pulmonary Disease

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