Mu 1A deficiency induces a profound increase in MPR300/IGF-II receptor internalization rate.
The mannose-6-phosphate/IGF-II receptor MPR300 mediates sorting of lysosomal enzymes from the trans-Golgi network to endosomes and endocytosis of hormones, for example, of IGF-II. We analyzed transport of MPR300 in mu1A-adaptin-deficient fibroblasts, which lack a functional AP-1 clathrin adaptor complex. In mu1A-adaptin-deficient fibroblasts, the homologous MPR46 accumulates in endosomes due to a block in retrograde transport to the trans-Golgi network. The MPR300-mediated endocytosis is markedly enhanced. We demonstrate that the seven-fold increase in endocytosis is not associated with an increased steady-state concentration of receptors at the plasma membrane, but with an increased internalization rate of MPR300. Internalization of other receptors that are also endocytosed by AP-2 is not affected. More MPR300 receptors are found in clathrin-coated pits of the plasma membrane, whereas outside coated-areas, more MPR300 are concentrated in clusters and all intracellular receptors reside in endosomes, which are in equilibrium with the plasma membrane. Thus AP-1-mediated transport of MPR300 from endosomes to the TGN controls indirectly the recycling rate of the receptor between the plasma membrane and endosomes.
Meyer
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Zentrum für Biochemie und Molekulare Zellbiologie, Biochemie II, Universität Göttingen, Heinrich-Düker-Weg 12, D-37073 Göttingen, Germany.
Eskelinen
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Guruprasad
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von Figura
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D033961:Adaptor Protein Complex 1; D033983:Adaptor Protein Complex mu Subunits; D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D002460:Cell Line; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D002966:Clathrin / Q000378:metabolism*; D004705:Endocytosis / Q000235:genetics; D011992:Endosomes / Q000235:genetics / Q000378:metabolism; D005089:Exocytosis / Q000235:genetics; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D021381:Protein Transport / Q000235:genetics; D017527:Receptor, IGF Type 2 / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics*
D033961:Adaptor Protein Complex 1; D033983:Adaptor Protein Complex mu Subunits; D033942:Adaptor Proteins, Vesicular Transport; C499063:Ap1m1 protein, mouse; D002352:Carrier Proteins; D002966:Clathrin; D008565:Membrane Proteins; D017527:Receptor, IGF Type 2; C499066:adaptor protein complex 1, mu 1 subunit