Back to the plasma membrane via recycling endosomes.Frontiers in Immunology | Immunotherapies and VaccinesSeptember 2013 | Volume 4 | Short article 267 |Blouin and LamazeTrafficking and signaling of IFNGRTable 1 | Morphological and molecular characteristics on the distinctive clathrin-independent endocytic pathways operating in mammalian cells. Endocytosis pathway Dynamin dependent Caveolae Vesicular Caveolin-1, -2, -3, cavin-1, -2, -3, -4, Src, PKC, actin IL2-R Vesicular RhoA, Rac1, PAK1, PAK2, cortactin, N-WASP actin , Dynamin independent CLIC-GEEC Tubular, crescent-like Arf6 Vesicular Arf6, actin Cdc42, Arf1, GRAF1, actin GPI-anchored proteins, fluid-phase uptake markers CD59, MHCI, carboxypeptidase E, -integrins, E-cadherin Flotillins Vesicular Flotillin-1,-2, actin GPI-anchored proteins, cholera toxin B subunit Toxins Tubular Actin Shiga toxin B subunit, cholera toxin B subunit, SV40, galectins Cholesterol, glycosphingolipids, AMF , lactosylceramide, CTxB, SV40, albumin IL2-R? c chain, Clostridium toxin, AMF Morphology Protein partners Cargo proteinsfamily of cytosolic proteins involved inside the assembly of caveolae at the plasma membrane have been recently identified. This family involves cavin-1 or polymerase I and transcript release issue (PTRF), cavin-2 or serum deprivation protein response (SDPR), cavin-3 or sdr-related gene solution that binds to C-kinase (SRBC), and cavin-4 or muscle restricted coiled oil protein (MURC) (27). Cavins interact with caveolins inside a lipid dependent manner and are required to maintain their LPAR1 Antagonist Biological Activity invaginated structure. The downregulation of cavins AT1 Receptor Inhibitor custom synthesis results in the disassembly of caveolae and to the release of totally free caveolins which can be subsequently degraded (28). The resembling shape of caveolae with CCP initially prompted investigators to analyze their possible ability to mediate endocytosis. Indeed, caveolae are 60?0 nm diameter cup-shaped membrane invaginations that bear a characteristic striated coat visible by electron microscopy (29). The GTPase dynamin, which mediates the mechanical release of CCP from the plasma membrane, has also been located in caveolae and is needed for caveolae detachment in the cell surface. But, little proof exists in support of a prominent part of caveolae in endocytic uptake in mammalian cells. Initial studies investigating the dynamics of caveolins by FRAP microscopy (fluorescence soon after photobleaching recovery) have revealed that the turnover of caveolins is very slow at the plasma membrane at steady state (30). Nonetheless, caveolar endocytosis can be effectively triggered by caveolin tyrosine phosphorylation and appears to become regulated by Src kinase, protein kinase C and actin (26). Even though caveolae possess the capability to recruit and concentrate a variety of signaling molecules and effectors, no caveolar distinct cargo has been identified thus far (31). However, various cargos might be located associated with caveolae and undergo caveolar endocytosis in a non-exclusive manner. This can be the case with all the autocrine motility aspect (AMF) and lactosylceramide that could attain the endoplasmic reticulum just after caveolar endocytosis (32, 33). It has been proposed that caveolae provide cargo to a specific endosomal compartment referred to as the caveosome (34). Even so, it has been lately shown that this compartment can be a likely artifact resulting from caveolin overexpression (35). Both IFNGR and IFNAR subunits display the standard endocytic codes recognizedby the clathrin-dependent endocytosis machinery,.
