Caveolae potocytosis

Caveolae, Folate Receptor, Receptor Clustering, and Potocytosis... 

E. J. Smart, D. C. Foster, Y. S. Ying, B. A. Kamen, and R. G. Anderson. Protein kinase C activators inhibit receptor-mediated potocytosis by preventing internalization of caveolae. J. Cell Biol. 124 307-313 (1994). 

Exposure to histamine [10 pM for 30-45 minutes recovery (in the presence of histamine) after 90 minutes] specifically blocks the uptake of 5-methyltetra-hydrofolate, a substance that is used to study potocytosis/caveolae uptake (48,64). Histamine might also be used to increase the permeability of the endothelium binding of histamine to its receptor leads to the contraction of the cytoskeleton and to the opening of intercellular junctions (65). 

In many studies, folate or folic acid (5nM) is applied to study caveolae-mediated endocytosis resp. potocytosis (27,119,120). 

Anderson RG. Potocytosis of small molecules and ions by caveolae. Trends Cell Biol 1993 3(3) 69-72. 

Non-clathrin-coated pit internalization can occur through smooth imagination of 150-300 nm vesicles or via potocytosis. This pathway has been shown to be involved in the transport of folate and other small molecules into the cytoplasm. Plasmids are taken up by muscles through the T-tubules system and caveolae via potocytosis. Muscle cells appear to take up plasmids through the T-tubule system and caveolae via potocytosis. Apart from coated or uncoated pit pathways, cells may also take up plasmid/cationic carrier complexes via plasma membrane destabilization. Particles greater than 200 nm in diameter are not... 

The function of caveolae includes the transport of molecules across these cells, but recently, it was shown that caveolae are also involved in potocytosis (the internalization of small molecules without the merging of an endocytotic vesicle with endosomes), signal transduction regulation, and cholesterol transport (41). 

The folate receptor facilitates the cellular uptake of folate and 5-methyltetrahydrofolate via receptor-mediated endocytosis at caveolae (caveolae are plasma membrane invaginations distinct from the classical clathrin-coated pits) (6). It has been hypothesized that the folate receptor is functionally coupled to an anion transporter to mediate cytosolic folate delivery by a process defined as potocytosis (6). More recent studies suggest that folate receptor endocytosis also occurs at clathrin-coated pits (7). Studies by Low and coworkers at Purdue University have shown that folate conjugates are also taken up by the folate receptor (8-10), but not by the reduced folate carrier. Figure 2 illustrates an endocytic pathway of the type envisioned for folate conjugates. Unfortunately, the subcellular transport pathway of the folate conjugates has been only partially characterized and may well be affected by the properties of the molecule attached to folate. 

GPI-anchored proteins play a role in a specialized form of endocytosis termed poto-cytosis. Potocytosis involves the capture and import of scarce extracellular molecules or ions against their concentration gradient through membrane invaginations, called caveolae, independent of the lysosomal pathway (reviewed in ref. [151]). Caveolae are 50 nm wide, flask-shaped structures coated with the 22kDa transmembrane protein, caveolin [152]. Caveolae contain clusters of GPI-anchored proteins, most notably, the... 

GPI anchors may extend the half-life of cell surfaee proteins whose functions do not involve internalization [18]. This is consistent with their presenee in eaveolae. Ligands are bound by GPI-anchored receptors in open eaveolae (reviewed in ref. [151]). Then eaveolae close and the ligand is released enzymatically or by low pH. A large concentration gradient results from the small volume of in the caveolae. The trapped molecules or ions flow down their concentration gradient into the cytoplasm through membrane carriers or transporters. GPI-anchored proteins are not internalized and when caveolae re-open they are presented for the next round of potocytosis. 

Vesicular transport occurs when a membrane completely surrounds a compound, particle, or cell and encloses it into a vesicle. When the vesicle fuses with another membrane system, the entrapped compounds are released. Endocytosis refers to vesicular transport into the cell, and exocytosis to transport out of the cell. Endocytosis is further classified as phagocytosis if the vesicle forms around particulate matter (such as whole bacterial cells or metals and dyes from a tattoo), and pinocy-tosis if the vesicle forms around fluid containing dispersed molecules. Receptor-mediated endocytosis is the name given to the formation of clathrin-coated vesicles that mediate the internalization of membrane-bound receptors in vesicles coated on the intracellular side with subunits of the protein clathrin (Eig. 10.14). Potocytosis is the name given to endocytosis that occurs via caveolae (small invaginations or caves ), which are regions of the cell membrane with a unique lipid and protein composition (including the protein caveolin-1). 

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