Phosphatidylinositol endocytosis

In the kiss-and-run mode exocytosis and endocytosis are directly coupled to each other, while in the case of classical complete vesicle fusion, exocytosis and slow clathrin-mediated endocytosis are timely and spatially separated. However, it appears that also in the latter case exocytosis and endocytosis occur coordinated, as both are stimulated by an increase of the cytoplasmic calcium concentration. It has been shown that after calcium entry the enzyme phospho-inositol-5 kinase Iy, which is enriched in the synapse, catalyzes the synthesis of phosphatidylinos-itol (4,5)-bisphosphate and that this mechanism is important for synaptic vesicle trafficking (Di Paolo et al. 2004). As many proteins involved in clathrin-mediated endocytosis are recruited to the plasma membrane by binding to phosphatidylinosi-tol (4,5)-bisphosphate (e.g., amphiphysin, dynamin, epsin, AP-180, and AP-2) it is attractive to speculate that elevated levels of calcium mediate the recruitment of en-docytic proteins to the plasma membrane by this mechanism. The increased level of phosphatidylinositol (4,5)-bisphosphate could be in part degraded by synaptojanin that thereby initiates the disassembly of the clathrin coat. Hence, calcium-induced transient increases in the level of phosphatidylinositol (4,5)-bisphosphate appear to play a central role for coupling exocytosis to clathrin-mediated endocytosis. In addition, it has been demonstrated that calcium also leads to the dephosphorylation of endocytic proteins as amphiphysin, dynamin, and synaptojanin, which in vitro is important for efficient coat assembly (Cousin and Robinson 2001). 

Micheva KD, Holz RW, Smith SJ (2001) Regulation of presynaptic phosphatidylinositol 4,5-biphosphate by neuronal activity. J Cell Biol 154 355-68 Micheva KD, Buchanan J, Holz RW, Smith SJ (2003) Retrograde regulation of synaptic vesicle endocytosis and recycling. Nat Neurosci 6 925-32... 

Itoh, T. and Takenawa, T., 2004, Regulation of endocytosis by phosphatidylinositol 4,5-bisphosphate and ENTH proteins. Curr. Top. Microbiol. Immunol. 282 31—47. 

One of the mechanisms of active reabsorption is endocytosis. Fluid phase endocytosis consists of the incorporation of fluid and solutes in vesicles formed at the base of the brush border membrane of the proximal tubular cells (Figure 1). A more efficient absorptive endocytosis involves first binding of a drug, such as the cationic aminoglycoside and/or may be cadmium [30, 31], to a carrier (phosphatidylinositol) located in the luminal membrane of the wall of the pi-nocytotic vesicle occurs followed by endocytosis and lysosomal fusion [32, 33]. 

Barbieri, M.A. Heath, C.M. Peters, E.M. Wells, A. Davis, J.N. Stahl, P.D. Phosphatidylinositol-4-phosphate 5-kinase-lj5 is essential for epidermal growth factor receptor-mediated endocytosis. J. Biol. Chem., 276, 47212-47216 (2001)... 

Synaptojanin 1, a phosphatidylinositol 5 -phosphatase involved in clathrin-mediated endocytosis [P. S. McPherson et al.. Nature 1996, 379, 353]. 

Sanlioglu S, Benson PK, Yang J, Atkinson EM, Reynolds T, Engelhardt JF. Endocytosis and nuclear trafficking of adeno-associated virus type 2 are controlled by racl and phosphatidylinositol-3 kinase activation. J Virol 2000 74 9184-9196. 

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