![]() ![]() Nevertheless, salient features of each form have been experimentally elucidated.īuilding on the classification of Doherty and McMahon (2009), CIE includes: caveolae-dependent endocytosis, clathrin-independent carrier/GPI-AP-enriched early endosomal compartment (CLIC/GEEC) pathway endocytosis, flotillin-dependent endocytosis, interleukin 2 receptor beta (IL-2Rβ) pathway endocytosis, Arf6-dependent endocytosis, phagocytosis, macropinocytosis, fast endophilin-mediated endocytosis, activity-dependent bulk endocytosis (ADBE), ultra-fast endocytosis (UFE), and massive endocytosis (MEND). ![]() Our present knowledge of CIE is chiefly limited by the lack of validated, path-specific molecular determinants and cargoes, as well as the existence of shared machinery between pathways and these factors confound interpretation of experimental results. Relative to CME, flux through CIE pathways accounts for only a small proportion of endocytic events in mammalian cells. In recent decades, a number of mechanisms of clathrin-independent endocytosis (CIE) have been discovered and characterized, some of which enable rapid, bulk internalization of membrane or otherwise facilitate acute responses. These events require membrane fluxes on the millisecond-to-second scale, which CME is not sufficient for. Some cellular functions, such as response to high intensity stimuli and directed migration, require rapid endocytosis of large patches of membrane. Clathrin-independent mechanisms of endocytosis Consequently, this usage is discouraged and a more descriptive schema-classification of endocytic routes by the identity of vesicular membrane components and cargoes-has been adopted. It is now appreciated, however, that removal of many plasmalemmal receptors is accomplished by multiple mechanisms that do not require clathrin. įor many years, the term “receptor-mediated endocytosis” was used synonymously with CME. CCVs can be further classified by the differential recruitment of over 50 adaptor and accessory proteins, as well as by the identity of their lipid and protein cargoes. Post-scission, the clathrin assemblies disintegrate, additional machinery is removed by uncoating factors, and uncoated vesicles deliver their contents to endosomes by fusion. CCPs progress through a series of well-defined morphological intermediates to form clathrin-coated vesicles (CCVs) upon scission from the plasma membrane. In CME, the assembly of clathrin triskelions on spherical membrane buds drives the formation of clathrin-coated pits (CCPs) 60–120 nm in diameter. This is in part due to the historical primacy of the characterization of clathrin-mediated endocytosis (CME) in 1976 but also in acknowledgement of its role as the primary endocytic route for cellular housekeeping functions. This review will discuss the role of endocytosis in the regulation of T cell function.Įndocytic pathways are often broadly classified by their dependence on the hexamer protein clathrin. Whereas endocytic regulation of some cellular functions, such as immune surveillance, has been extensively described in some immune cell types (such as dendritic cells and macrophages), its functional importance in T cells has been less appreciated. Other forms are limited to and adapted for specific cell types or lineage states. Distinct forms of endocytosis have evolved in eukaryotes, with clathrin-mediated endocytosis (CME) being the most well-described and universal type. Functions regulated at least in part by endocytosis include: signal transduction, membrane composition, mitosis, adhesion, lipid homeostasis, motility, and cell morphogenesis. Co-evolution of endocytosis and cellular endosymbiosis, the state of one cell living mutualistically within another, may have significantly contributed to the complexity of eukaryotic cells. In addition to enabling the internalization of extracellular macromolecules, endocytosis permits the compartmentalization of chemistry within cells. Endocytosis, the generation of internal membranes from the plasma membrane by invagination and vesicle scission, facilitates a range of diverse cellular processes in eukaryotes. ![]()
0 Comments
Leave a Reply. |