title: Microdomains in the membrane landscape shape antigen-presenting cell function.
abstract: The plasma membrane of immune cells is a highly organized cell structure that is key to the initiation and regulation of innate and adaptive immune responses. It is well-established that immunoreceptors embedded in the plasma membrane have a nonrandom spatial distribution that is important for coupling to components of intracellular signaling cascades. In the last two decades, specialized membrane microdomains, including lipid rafts and TEMs, have been identified. These domains are preformed structures ("physical entities") that compartmentalize proteins, lipids, and signaling molecules into multimolecular assemblies. In APCs, different microdomains containing immunoreceptors (MHC proteins, PRRs, integrins, among others) have been reported that are imperative for efficient pathogen recognition, the formation of the immunological synapse, and subsequent T cell activation. In addition, recent work has demonstrated that tetraspanin microdomains and lipid rafts are involved in BCR signaling and B cell activation. Research into the molecular mechanisms underlying membrane domain formation is fundamental to a comprehensive understanding of membrane-proximal signaling and APC function. This review will also discuss the advances in the microscopy field for the visualization of the plasma membrane, as well as the recent progress in targeting microdomains as novel, therapeutic approach for infectious and malignant diseases.
authors.affiliation: 1.Nijmegen Centre for Molecular Life Sciences/278 TIL, Radboud University Medical Centre, Geert Grooteplein 28, 6525GA, Nijmegen, The Netherlands. a.vanspriel@ncmls.ru.nl.
authors.forename: Malou
authors.initials: M
authors.lastname: Zuidscherwoude
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: de Winde
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cambi
authors.forename: Annemiek B
authors.initials: AB
authors.lastname: van Spriel
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology*; D006801:Humans; D007154:Immune System Diseases / Q000276:immunology / Q000473:pathology / Q000628:therapy; D021962:Membrane Microdomains / Q000737:chemistry / Q000276:immunology*; D058990:Molecular Targeted Therapy; D015398:Signal Transduction / Q000276:immunology
keywords: B cell antigen receptor; major histocompatibility complex class II; pattern recognition receptor; signal transduction; tetraspanin