The Role of Dynamin in Caveolar Function

From the sections above, it is clear that dynamin is central in the discussions on caveolar endocytosis, and this GTP-binding protein therefore warrants further attention in this chapter. It is well established that dynamin plays a role in the final scission of clathrin-coated vesicles to form free endocytic vesicles [94,95], and it has also been reported to be important for the fission of caveolae [28,29]. However, the role of dynamin associated with caveolae can be complex. Dynamin is an actin-interacting protein which, for example, binds to cortactin. Indeed, recently dynamin was found to be involved in the regulation of actin polymerization during micropinosome comet formation - that is, the formation of rapidly moving vesicles propelled forward by an actin treadmilling machine [96]. Additionally, caveolin interacts with the actin cytoskeleton via filamin, and reorganization of the actin cytoskeleton leads to redistribution of caveolae [39]. Depolymerization of the actin cytoskeleton with cytochalasin D leads to an increase in caveolar mobility, and it has therefore been suggested that the normal immobility of caveolae is due to an anchoring role of actin filaments [31]. Dynamin could be a partner in such stabilization of caveolae. As mentioned above (see Section 4.4), Pelkmans et al. [53] found a pronounced SV40 virus-induced reorganization of the actin cytoskeleton and showed that dynamin is transiently recruited to SV40 virus-containing caveolae, which are subsequently internalized. Hence, it could be speculated that the internalization of caveolae, induced for instance by SV40 virus or okadaic acid [62], leads to a reorganization of the actin cytoskeleton mediated by dynamin. In fact, cytochalasin D inhibits the okadaic acid-stimulated uptake of caveolae [62], and there is an increasing body of evidence that actin plays a key role in endocytosis [62,97-99]. Therefore, the possible association of dynamin with caveolae does not per se indicate that these caveolae are going to pinch off unless other processes such as actin reorganization have also been initiated in response to a specific stimulation. In agreement with this and, as pointed out above, we found no accumulation of caveolae at the plasma membrane in cells expressing dominant-negative dynamin, as would have been expected if dynamin was constitutively mediating scission of caveolae (our unpublished observations).

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Essentials of Human Physiology

Essentials of Human Physiology

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