Mutations in the cytoplasmic domain of the 275 kd mannose 6-phosphate receptor differentially alter lysosomal enzyme sorting and endocytosis

Lobel, Peter; Fujimoto, K; Ye, Richard D.; Griffiths, Gareth; Kornfeld, Stuart

doi:10.1016/0092-8674(89)90793-9

Cited by 269 publications

(179 citation statements)

References 42 publications

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“…Briefly, CD8 WT (CD8-WT) contains no known sorting signals in its cytoplasmic tail, is therefore not subject to endocytosis and is resident at the plasma membrane (28). CD8-cation-independent mannose 6-phosphate receptor (CIMPR) contains the cytoplasmic domain of CIMPR, a wellcharacterized cargo that is efficiently internalized in clathrincoated vesicles before being trafficked to the trans-Golgi network (TGN) and a subset of late endosomes, via sorting and recycling endosomes (32,33). The remaining constructs contain "designer" tails that represent three well-established endocytic motifs: YXXΦ (CD8-YAAL), [DE]XXXL[LI] (CD8-EAAALL), and FXNPXY (CD8-FANPAY), all transposed on a background of eight alanines (CD8-8xA) (28).…”

Section: Resultsmentioning

confidence: 99%

Clathrin-mediated endocytosis is inhibited during mitosis

Fielding

Willox

Okeke

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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A long-standing paradigm in cell biology is the shutdown of endocytosis during mitosis. There is consensus that transferrin uptake is inhibited after entry into prophase and that it resumes in telophase. A recent study proposed that endocytosis is continuous throughout the cell cycle and that the observed inhibition of transferrin uptake is due to a decrease in available transferrin receptor at the cell surface, and not to a shutdown of endocytosis. This challenge to the established view is gradually becoming accepted. Because of this controversy, we revisited the question of endocytic activity during mitosis. Using an antibody uptake assay and controlling for potential changes in surface receptor density, we demonstrate the strong inhibition of endocytosis in mitosis of CD8 chimeras containing any of the three major internalization motifs for clathrin-mediated endocytosis (YXXΦ, [DE]XXXL[LI], or FXNPXY) or a CD8 protein with the cytoplasmic tail of the cationindependent mannose 6-phosphate receptor. The shutdown is not gradual: We describe a binary switch from endocytosis being "on" in interphase to "off" in mitosis as cells traverse the G 2 /M checkpoint. In addition, we show that the inhibition of transferrin uptake in mitosis occurs despite abundant transferrin receptor at the surface of HeLa cells. Our study finds no support for the recent idea that endocytosis continues during mitosis, and we conclude that endocytosis is temporarily shutdown during early mitosis.

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Section: Resultsmentioning

confidence: 99%

Clathrin-mediated endocytosis is inhibited during mitosis

Fielding

Willox

Okeke

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…Furthermore, cytoplasmic domains contain essential information for endocytosis of membrane proteins in coated pits (Chen et al, 1990;Johnson et al, 1990;Canfield et al, 1991) and for shuttling of mannose 6-phosphate receptors between the trans-Golgi network and prely- sosomal compartments (Lobel et al, 1989). It therefore seemed possible that the signals directing membrane proteins to secretory storage granules might also be located in their cytoplasmic domains.…”

Section: Att20mentioning

confidence: 99%

Cytoplasmic domain of P-selectin (CD62) contains the signal for sorting into the regulated secretory pathway.

Disdier

Morrissey

Fugate

et al. 1992

MBoC

155

111

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P-selectin (CD62), formerly called GMP-140 or PADGEM, is a membrane protein located in secretory storage granules of platelets and endothelial cells. To study the mechanisms responsible for the targeting of P-selectin to storage granules, we transfected its cDNA into COS-7 and CHO-Ki cells, which lack a regulated exocytic pathway, or into AtT20 cells, which are capable of regulated secretion. P-selectin was expressed on the plasma membrane of COS-7 and CHO-Kl cells but was concentrated in storage granules of AtT20 cells. Immunogold electron microscopy indicated that the electron-dense granules containing P-selectin in AtT20 cells also stored the endogenous soluble hormone ACTH. Activation of AtT20 cells with 8-Br-cAMP increased the surface expression of P-selectin, consistent with agonist-induced fusion of granule membranes with the plasma membrane. Deletion of the last 23 amino acids of the 35-residue cytoplasmic domain resulted in delivery of Pselectin to the plasma membrane of AtT20 cells. Replacement of the cytoplasmic tail of tissue factor, a plasma membrane protein, with the cytoplasmic domain of P-selectin redirected the chimeric molecule to granules. We conclude that the cytoplasmic domain of P-selectin is both necessary and sufficient for sorting of membrane proteins into the regulated pathway of secretion.

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“…Presumably, membrane proteins returning to the TGN from late endosomes would be sorted and exit the TGN in the same manner as newly synthesized molecules . If CI-MPR and LDL-R are not sorted from each other in endosomes, the observed accumulation of CI-MPR in late endosomes may be due solely to selective targeting of CI-MPR from the TGN directly to endosomes, a sorting event that is well documented and clearly signal mediated (27,35) . The rapidly internalized fraction ofthe receptor found on the cell surface, up to 10% of the total at steady state, may be the pool that is "missortnd" upon exit from the TGN into the constitutive secretory pathway, or delivered to early endosomes (38).…”

Section: A Modelfor Traffic Through Late Endosomesmentioning

confidence: 99%

Low density lipoprotein receptor and cation-independent mannose 6-phosphate receptor are transported from the cell surface to the Golgi apparatus at equal rates in PC12 cells

Kelly

1992

The Journal of Cell Biology

146

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Abstract. Efficient transport of cell surface glycoproteins to the Golgi apparatus has been previously demonstrated for a limited number of proteins, and has been proposed to require selective sorting in the endocytic pathway after internalization . We have studied the endocytic fate of several glycoproteins that accumulate in different organelles in a variant clone of PC12, a regulated secretory cell line. The cationindependent mannose 6-phosphate receptor and the low density lipoprotein receptor, both rapidly internalized from the cell surface, and the synaptic vesicle membrane protein synaptophysin, were transported to the Golgi apparatus with equivalent, nonlinear kinetics. Transport to the Golgi apparatus (t 1/2 = 2.5-3.0 h) was several times fäster than turnover of these proteins (ti/2 > 20 h), indicating that transport of these proteins to the Golgi apparatus occurred on average

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Mutations in the cytoplasmic domain of the 275 kd mannose 6-phosphate receptor differentially alter lysosomal enzyme sorting and endocytosis

Cited by 269 publications

References 42 publications

Clathrin-mediated endocytosis is inhibited during mitosis

Clathrin-mediated endocytosis is inhibited during mitosis

Cytoplasmic domain of P-selectin (CD62) contains the signal for sorting into the regulated secretory pathway.

Low density lipoprotein receptor and cation-independent mannose 6-phosphate receptor are transported from the cell surface to the Golgi apparatus at equal rates in PC12 cells

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