摘要：

Signals triggered through the receptors on the plasma membrane of innate and adaptive immune cells are regulated in space and time (spatial-temporal). While the basic understanding of the temporal events of the signaling cascade initiated at the plasma membrane has remained a longstanding focus, the insights into the spatial distribution of signaling proteins and their reorganization during signaling process is under intense investigation. It has been proposed that membrane rafts on the plasma membrane provide a platform for the organization of signaling molecules during initiation and/or regulation of membrane signaling in a variety of cell types. While the merit of methods to investigate these nanometer size domains are being debated, the details of their role in signal transduction remain a hot topic of investigation. In a Keystone Symposium on Lipid Rafts and Cell Function in 2006 membrane rafts were defined as small (10-200 nm), heterogeneous, highly dynamic, sterol- and sphingolipid-enriched domains that compartmentalize cellular processes. Small rafts can sometimes be stabilized to form larger platforms through protein-protein and protein-lipid interactions. Small dynamic and compositionally heterogeneous nature of membrane rafts has been proposed to be central to their functional role. A number of signaling proteins are either housed in membrane rafts or traffic through these cholesterol-rich nano-domains during cell signaling. It has been suggested that small and dynamic nature of each membrane raft on an un-stimulated plasma membrane may be key to its existence as incomplete signaling unit and therefore contributing to the quiescent state of the cell. Coalescence of membrane rafts on the plasma membrane during cell stimulation allow congregation of signaling proteins in the rafts, thereby promoting their molecular interactions and generation of signals that cascade to the cell interior. Over the past decade it has become increasingly clear that signaling through pattern recognition receptors (PRR) in innate immune cells (e.g., dendritic cells (DC) and macrophages) and multi-chain antigen receptor in cells of adaptive immunity (e.g., B and T cells) either get initiated in membrane rafts or propagated through these nano-domains. While the details related to the involvement of membrane rafts are currently being worked-out, this new paradigm in cell signaling has direct implications in initiation/regulation of immune response during normal and abnormal immune responses. This thematic issue on Membrane Rafts and Signaling reviews some important aspects of raft biology and provides an additional possibility of rational drug design to interrupt or modulate signals in immune cells. Kazuhisa Iwabuchi and colleagues from Juntendo University, Graduate School of Medicine in Chiba, focus their review on Lactosylceramide (LacCer, CDw17), an innate immune receptor expressed on neutrophils, that bind a variety of microorganisms, including Bordetella pertussis, Helicobacter pylori, and Candida albicans. This review also provides insights into co-localization of LacCer and a Src kinase, lyn, in membrane rafts and its role in superoxide generation, chemotaxis, and nonopsonic phagocytosis. Katharina Gaus and her colleagues from University of New South Wales in Sydney discuss the role of membrane rafts in phagocytosis mediated through Fc receptors in macrophages, another component cell of innate immunity. Helper CD4+ T cells orchestrate adaptive immune response by providing requisite help to other immune cells. CD4+ T cells are capable of rendering this help only after sensing a pathogen or allergen presented to them by antigen presenting cells. The two interacting cells at their contact site generate immunological synapse (IS). Immune receptors that drive T cell adhesion and activation show remarkable organization at the IS. Recent findings provide evidence for condensation of T cell membrane at the contact site with antigen presenting cells during these cellular interactions. Katharina Gaus and her colleagues high

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