Caveolin-mediated endocytosis Sample Clauses

Caveolin-mediated endocytosis. Similar to the clathrin-coated vesicles, caveolae vesicles also originate from cholesterol-enriched invaginations of the plasma membrane. They invaginated as flask-shaped vesicles within the plane of the plasma membrane, or as detached vesicles. In addition, caveolae can fuse to form grape-like structures and tubules with sizes larger than 100 nm (Xxxxx, X.X. et al., 1999, Pelkmans, X. et al., 2001). Caveolae are mainly composed of cholesterol and sphingolipids and accumulate cholesterol binding-proteins known as caveolins, on the cytosolic face of the vesicles (Xxxxx, X.X. xx al., 1999, Xxxxxxx, X. et al., 2001, Xxxxxx, X. et al., 2002). Caveolae play a role in endocytosis of certain viruses such as simian virus 40 (SV40), as well as some bacteria and bacterial toxins such as cholera toxin (Khalil, I.A. et al., 2006) and like the clathrin pathway, calveolae require GTPases activity for the pinch off of vesicles. After internalisation, caveolae-derived vesicles fuse with caveosomes (Xxxxxxx, X.X. and X. Xxxxxxxxxx-Xxxxxxxx, 2001, Pelkmans, X. et al., 2002), which are pre- existing, stable, organelles with a neutral pH and it is believed that this uptake mechanism does not lead to lysosomal degradation (Xxxxxx, X.X., 2004). Macromolecules internalized via this route are transported to the endoplasmic reticulum (ER) (Pelkmans, X. et al., 2001) or to the trans-Golgi network (TGN) (Xxxxxx, X.X. and X. Xxxxxx, 2005) and therefore avoid lysosomal degradation. Due to its non-degradative nature (Ferrari, X. et al., 2003, Xxxxxx, X. et al., 2002), caveolar endocytosis represents an attractive pathway for gene delivery, even though this process is considered slow and has a small phase volume making it unlikely to be a primary uptake route. This uptake is also energy dependent so it can be inhibited by lowering temperature or by ATP depletion. In addition, drugs that specifically bind, sequester, or deplete cholesterol such as filipin, nystatin, and methyl-β-cyclodextrin, respectively, inhibit internalization by the caveolae (Lamaze, C. and X.X. Xxxxxx, 1995, Xxxxxxxxx, X.X. xx al., 1994). The caveloae pathway is actin-dependent and therefore drugs that affect the actin cytoskeleton such as cytochalasins are used to inhibit caveloae pathway without affecting the clathrin-mediated endocytosis, although these drugs do also inhibit macropinocytosis (Xxxxxx, X.X., 2004).
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