Receptors mannose-6-phosphate

The mannose 6-phosphate receptor is the cargo/coat-receptor for trans-Golgi network (TGN)-derived cla-thrin vesicles. The receptor recognizes the mannose 6-phosphate tag of lysosomal hydrolases on the luminal side and the adaptor-1 complex of clathrin on the cytoplasmic face. 

Munier-Lehmann, H., Mauxion, F. and Hoflack, B. Function of the two mannose 6-phosphate receptors in lysosomal enzyme transport. Biochem. Soc. Trans. 24 133-136,1996. 

Figure 14.7 Models of phosphorylated high-mannose M7 and a glycopeptide mimic obtained by MD calculation showing similar conformations. They are seen from the point of interaction with the mannose-6-phosphate receptor. Disaccharide phosphates are emphasized as spheres.76...

Recently another signal, the phenylalanine-tryptophan motif (or the motif containing two aromatic residues, such as (F/Y)X(F/Y), in yeast), was shown to direct some proteins including cation-dependent mannose 6-phosphate receptor (see Section IIIJ,2) from endosomes to the TGN (Schweizer et al., 1997 Burd et al., 1998). Most probably, it is used for the (retrograde) recycling processes. A putative coat complex was also discovered and named retromer (Seaman et al., 1998). 

Ludwig, T., Le Borgne, R., and Hoflack, B. (1995). Roles for mannose-6-phosphate receptors in lysosomal enzyme sorting, IGF-II binding and clathrin-coat assembly. 

Schweizer, A., Kornfeld, S., and Rohre, J. (1997). Proper sorting of the cation-dependent mannose 6-phosphate receptor in endosomes depends on a pair of aromatic amino acids in the cytoplasmic tail. Proc. Natl. Acad. Sci. U.S.A. 94, 14471-14476. 

Couce M, Weatherington A, McGinty JE. 1992. Expression of insulin-like growth factor-II (IGF-II) and IGE-II/Mannose-6-phosphate receptor in the rat hippocampus an in situ hybridization and immunocytochemical study. Endocrinology 131 1636-1642. 

Hawkes C, Kar S. 2003. Insulin-like growth factor-II/mannose-6-phosphate receptor widespread distribution in neurons of the central nervous system including those expressing cholinergic phenotype. J Comp Neurol 458 113-127. 

Hawkes C, Kar S. 2004. The insulin-like growth factor-II/ mannose-6-phosphate receptor structure, distribution and function in the central nervous system. Brain Res Rev 44 117-140. 

Hawkes C, Jhamandas JH, Harris K, Fu J, Mac Donald RG, et al. 2006. Single transmembrane domain insulin-like growth factor-II/mannose-6-phosphate receptor regulates central cholinergic function by activating a G-protein-sensi-tive, protein kinaseC-dependent pathway. J Neurosci 26 585-596. 

Hille-Rehfeld A. 1995. Mannose 6-phosphate receptors in sorting and transport of lysosomal enzymes. Biochim Biophys Acta 1241 177-194. 

IGFII/M6P insulin-like growth factor II/mannose-6-phosphate receptor... 

A number of carbohydrate recognition domains (CRDs) of animal lectins are known to exist as clusters. ASGP-Rs exist as bundle of hexamers, mannose 6-phosphate receptor and galectin-3 are known as dimers, while mannose binding proteins and receptors form multiple CRDs [31]. 

G. Griffiths, B. Hoflack, K. Simons, I. Mellman and S. Komfeld, The mannose 6-phosphate receptor and the biogenesis of lysosomes, Cell 52 (1988) 329-341. 

P. J. De Bleser, C. D. Scott, T. Niki, G. Xu, E. Wisse, and A. Geerts, Insulin-like growth factor II/mannose 6-phosphate-receptor expression in liver and serum during acute CC14 intoxication in the rat, Hepatology 23 1530-1537 (1996). 

Urayama, A., Grubb, J. H., Sly, W. S. and Banks, W. A. (2004). Developmen-tally regulated mannose 6-phosphate receptor-mediated transport of a... 

Lysosomal proteins are targeted to the lysosomes via the addition of a mannose 6-phosphate signal that is added in the ds-compartment of the Golgi and is recognized by a receptor protein in the frans-compartment of the Golgi. The protein is then transported by specialized vesicles to a late endosome that later matures into a lysosome. The mannose 6-phosphate receptor recycles back to the Golgi for re-use. 

Not all lysosomal proteins take the normal route of protein targeting some end up being exported by the cell and must be retrieved. This scavenger pathway works as follows. The lysosomal glycoprotein binds to mannose 6-phosphate receptors in the plasma membrane and is internalized again by endocytosis (Fig. 5). This process, called receptor-mediated endocytosis, creates an endocytic vesicle (or endosome) that then delivers the lysosomal protein to the lysosome by fusion (see Topic E4). 

In the confocal microscopy experiment, it is recommended to include a negative control. This could be done by incubating cells with phages at 4°C, which should minimize internalization and thus only result in cell surface localization. In addition, endocytosis inhibitors could be used to monitor this event. The subcellular localization could be assessed by co-staining with antibodies that are reactive with different intracellular compartments. For instance, early endosome can be visualized by an EEA1 antibody, whereas late endosomes can be stained by an antibody against the mannose-6-phosphate receptor. 

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