Folate receptor

While the fluid mosaic model of membrane stmcture has stood up well to detailed scrutiny, additional features of membrane structure and function are constantly emerging. Two structures of particular current interest, located in surface membranes, are tipid rafts and caveolae. The former are dynamic areas of the exo-plasmic leaflet of the lipid bilayer enriched in cholesterol and sphingolipids they are involved in signal transduction and possibly other processes. Caveolae may derive from lipid rafts. Many if not all of them contain the protein caveolin-1, which may be involved in their formation from rafts. Caveolae are observable by electron microscopy as flask-shaped indentations of the cell membrane. Proteins detected in caveolae include various components of the signal-transduction system (eg, the insutin receptor and some G proteins), the folate receptor, and endothetial nitric oxide synthase (eNOS). Caveolae and lipid rafts are active areas of research, and ideas concerning them and their possible roles in various diseases are rapidly evolving. 

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Wiener and co-workers used folic acid-conjugated Gd(DTPA)-PAMAM dendrimers for visualizing the high-affinity folate receptor, overexpressed in many tumors.201 The contrast agent accumulated in the cells, resulting in a remarkable contrast enhancement on 7)-weighted images. 

Fig. 6.22. Folate-FRET sensor structure and its application to measure disulfide bond reduction in endosomes. The molecule contains the folate moiety which is recognized by the folate receptor situated at the plasma membrane. This recognition leads to endocytosis and after some time to cleavage of the probe. 

Fig. 11 Above Folate receptor-mediated targeting and SWNT-mediated delivery of structure 1 by endocytosis. Below. Structure 1. (Adapted from [60]).

Ross, J.F., Chaudhuri, P.K., and Ratnam, M. (1994) Differential regulation of folate receptor isoforms in normal and malignant tissues in vivo and established cell lines. Physiologic and clinical implications. Cancer 73, 2432-2443. 

Shukla, S., Wu, G., Chatterjee, M., Yang, W., Sekido, M., Diop, L.A., Muller, R., Sudimack, J.J., Lee, R.J., Barth, R.F., and Tjarks, W. (2003) Synthesis and biological evaluation of folate receptor-targeted boro-nated PAMAM dendrimers as potential agents for neutron capture therapy. Bioconjugate Chem. 14, 158-167. 

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

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Stevens PJ, Sekido M, Lee RJ. A folate receptor-targeted lipid nanoparticle formulation for a lipophilic paclitaxel prodrug. Pharm Res 2004 21 2153. 

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Rothenberg KG, Ying YS, Kolhouse JF, Karmen BA, Anderson RG. The glycophospholipid-linked folate receptor internalizes folate without entering the clathrin-coated pit pathway. J Cell Biol 1990 110 637-649. 

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