In addition to reaching the TGN, internalized CT is also found in caveosomes , the organelle reached by internalized SV40 virus . The caveosome is a non-acidic, caveolin-associated compartment that does not stain for EEA1, a marker of early endosomes reached by the clathrin-dependent endocytic pathway. Moreover, caveosomes do not accumulate Lysotracker, a lysosomal marker, and they do not stain for TGN46 and mannosidase II, both of which are Golgi markers . Evidence that the clathrin-dependent endosome pathway and the caveolin-dependent caveosome pathway somehow merge are accumulating [91,92]. Moreover, in studies with SV40 virus and CT it was recently reported that these caveolar markers are transported by a Rab5-dependent pathway to early endosomes and that early endo-somes and caveosomes may even communicate via this Rab5 pathway . An important difference between the two ligands is that the Rab5-dependent step is required for CT transport to the Golgi complex, but not for SV40 entry into the ER.
These studies further stress the important notion that because a certain ligand initially is seen in caveolae, and later on also in intracellular compartments associated with caveolin, the ligand has not necessarily been internalized and transported to the compartment by caveolae. For instance, transforming growth factor beta (TGFb) was found to localize to both rafts/caveolae and clathrin-coated pits at the cell surface . Moreover, after internalization, TGFb was seen in caveolin-positive vesicles as well as in vesicles staining for EEA1. It was therefore concluded that two endocytic pathways for TGFb were operating in parallel: one mediated by clathrin-coated pits and vesicles and leading to endosomes and subsequently to TGFb signaling; and one mediated by rafts/caveolae leading to caveolin-positive vesicles (caveosomes?) involved in receptor degradation and turnover. However, caveolae could in fact bind TGFb without being involved in endocytosis, and all internalized receptors could have been taken up by endocytic noncaveolar rafts or clathrin-dependent endocytosis, leading to endosomes. These endosomes, in turn, may exchange material with caveolin-positive vesicles or even with caveosomes via intracellular, caveolin-associated carrier vesicles.
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This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.