Endocytosis pathways in endothelium: how many?
Endocytosis pathways in endothelium: how many?
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内皮细胞的内吞途径：有多少？
DOI：
10.1152/ajplung.00533.2005
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Stan,RaduV
中科院分区：
文献类型：
--
作者：
Stan,RaduV
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VASCULAR ENDOTHELIUM is a cellular monolayer with the organization of a simple squamous epithelium that lines the entire cardiovascular system and constitutes a regulatable barrier between blood and tissues (9, 17). By its location, it is easily accessible to blood-borne drugs or imaging agents, which would target the endothelium itself or be destined to transport to the underlying tissues (13).For a drug or imaging molecule/complex to be targeted to a specific vascular bed, it requires binding to a molecule expressed specifically on the surface of the endothelial cells (EC) in that territory, in either normal or pathological conditions. If uptake is desired, the surface molecule should undergo endocytosis, a term that describes the process of uptake of material into cells (2, 10). If the drug molecule/complex requires delivery to the underlying tissue, it can reach it by either locally manipulating the paracellular pathway or taking advantage of one of the transcellular pathways described (13). The latter are either pores that cut across EC, such as fenestrae, vesiculo vacuolar organelles, and transendothelial channels (specific to the EC in select vascular beds but rather poorly described in terms of components and regulation), or are vesicular in nature (17, 18). The vesicular pathway or transcytosis is common to all epithelia (to which endothelium belongs) and is defined as the process by which large molecules are transported across cellular barriers in membrane-bounded vesicular carriers (21). It encompasses the uptake of the molecule at one endothelial front by endocytosis, transport across the cell via vesicular carriers, and exocytosis at the opposite front. From these, it is readily clear that endothelial endocytosis is one of the critical steps to be reckoned with in the rational design of drug targeting. Endocytosis can occur via diverse mechanisms, which could be divided into two classes: phagocytosis and pinocytosis (reviewed in Refs. 2, 5, and 10). Phagocytosis (in Greek “to eat”) refers to internalization of particulates and occurs rarely in EC. Pinocytosis (in Greek “to drink”) defines the internalization of soluble molecules as bulk or via interactions with their surface receptors. To date, there are several internalization mechanisms that have been described to participate in pinocytosis: clathrin-mediated uptake (CME), caveolae-mediated uptake (CavME), clathrin-and caveolae-independent internalization (CLIC), and macropinocytosis (occurs rarely in quiescent endothelium in situ, if ever). There are several clathrin-and caveolae-independent uptake pathways or CLIC pathways (5) with respect to their dependence on dynamin, a large GTPase involved in the fission of vesicles from the plasma membrane (8). One pathway is dynamin independent (CLIC)(5), has the ability to internalize large molecular weight ligands, and has been shown to mediate the uptake of glycosylphosphatidylinositol-linked proteins (4, 16). Another path-