Endocytosis stimulation

LDL (apo B-lOO, E) receptors occur on the cell surface in pits that are coated on the cytosolic side of the cell membrane with a protein called clathrin. The glycoprotein receptor spans the membrane, the B-lOO binding region being at the exposed amino terminal end. After binding, LDL is taken up intact by endocytosis. The apoprotein and cholesteryl ester are then hydrolyzed in the lysosomes, and cholesterol is translocated into the cell. The receptors are recycled to the cell surface. This influx of cholesterol inhibits in a coordinated manner HMG-CoA synthase, HMG-CoA reductase, and, therefore, cholesterol synthesis stimulates ACAT activ-... 

Evidence is also growing that PsPc plays an important role in copper homeostasis, in particular at the pre-synaptic membrane that it may be involved in triggering intracellular calcium signals and that it may play a neuroprotective role in response to copper and oxidative stress (Figure 18.6). Exposure of neuroblastoma cells to high Cu(II) concentrations stimulated endocytosis of PsPc, whereas deletion of the four octarepeats or mutation of the histidine residues in the central two repeats abolished endocytosis of PsPc (see Chapter 8). 

E. B. Malarkey, R. C. Reyes, B. Zhao, R. C. Haddon, V. Parpura, Water soluble single-walled carbon nanotubes inhibit stimulated endocytosis in neurons, Nano Letters, vol. 8, pp. 3538-3542, 2008. 

Hicke, L. and Riezman, H. Ubiquitination of a yeast plasma membrane receptor signals its ligand-stimulated endocytosis. Cdl 1996, 84, 277-87. 

Clathrin-mediated endocytosis involves the internalization of transmembrane receptor-ligand complexes stimulating the formation of a coated pit that eventually buds off the membrane to form an intracellular endocy-totic vesicle. This process is dependent on the protein clathrin that is recruited to the membrane and forms a cage-like structure around the forming pit. Internalization via clathrin-dependent pathway allows the uptake of particles approximately 120nm in size (63-65). Once internalized, the clathrin coating disassociates from the endosome to be recycled and to allow the endosome to fuse with an intracellular compartment, usually a... 

The apical clathrin-independent pathway is selectively stimulated by reagents that raise intracellular cAMP, such as mastoparan, fluoride, or cholera toxin. Apical endocytosis is also stimulated by brefeldin A (BFA) (106) or by PMA. For an excellent review on transcytosis, see Tuma and Hubbard (138). 

Holm PK, Eker P, Sandvig K, van Deurs B. Phorbol myristate acetate selectively stimulates apical endocytosis via protein kinase C in polarized cells. Exp Cell Res 1995 217(1) 157-168. 

VLDLs, IDLs, and LDLs are closely related to one another. VLDLs formed in the liver (see p. 312) transport triacylglycerols, cholesterol, and phospholipids to other tissues. Like chylomicrons, they are gradually converted into IDL and LDL under the influence of lipoprotein lipase [1]. This process is also stimulated by HDL. Cells that have a demand for cholesterol bind LDL through an interaction between their LDL receptor and ApoB-100, and then take up the complete particle through receptor-mediated endocytosis. This type of transport is mediated by depressions in the membrane ( coated pits"), the interior of which is lined with the protein clathrin. After LDL binding, clathrin promotes invagination of the pits and pinching off of vesicles ( coated vesicles"). The clathrin then dissociates off and is reused. After fusion of the vesicle with ly-sosomes, the LDL particles are broken down (see p. 234), and cholesterol and other lipids are used by the cells. 

Panlp- Panlp in yeast, and its mammalian homologue, EGFR protein substrate 15 (EpslS), are essential for normal endocytosis (Carbone et al. 1997 Benmerah et al. 1998 Wendland and Emr 1998). Although these proteins are associated with clathrin complexes and genetic evidence raised the possibility that Panlp may act as an adaptor connecting RspSp to potential ubiquitination substrates, physical associations between RspSp and Panlp have not been detected. In mammalian cells, EpslS is tyrosine-phosphorylated and mono-ubiquitinated upon EGF stimulation (van Delft et al. 1997). The tyrosine-phosphorylation of the protein may play a role in... 

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