A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
mu 1A deficiency induces a profound increase in MPR300/IGF-II receptor internalization rate
Tekijät: Meyer C, Eskelinen EL, Guruprasad MR, von Figura K, Schu P
Kustantaja: COMPANY OF BIOLOGISTS LTD
Julkaisuvuosi: 2001
Journal: Journal of Cell Science
Tietokannassa oleva lehden nimi: JOURNAL OF CELL SCIENCE
Lehden akronyymi: J CELL SCI
Vuosikerta: 114
Numero: 24
Aloitussivu: 4469
Lopetussivu: 4476
Sivujen määrä: 8
ISSN: 0021-9533
Tiivistelmä
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.
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.
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