mu1A-adaptin-deficient mice: lethality, loss of AP-1 binding and rerouting of mannose 6-phosphate receptors.
The heterotetrameric AP-1 complex is involved in the formation of clathrin-coated vesicles at the trans-Golgi network (TGN) and interacts with sorting signals in the cytoplasmic tails of cargo molecules. Targeted disruption of the mouse mu1A-adaptin gene causes embryonic lethality at day 13.5. In cells deficient in micro1A-adaptin the remaining AP-1 adaptins do not bind to the TGN. Polarized epithelial cells are the only cells of micro1A-adaptin-deficient embryos that show gamma-adaptin binding to membranes, indicating the formation of an epithelial specific AP-1B complex and demonstrating the absence of additional mu1A homologs. Mannose 6-phosphate receptors are cargo molecules that exit the TGN via AP-1-clathrin-coated vesicles. The steady-state distribution of the mannose 6-phosphate receptors MPR46 and MPR300 in mu1A-deficient cells is shifted to endosomes at the expense of the TGN. MPR46 fails to recycle back from the endosome to the TGN, indicating that AP-1 is required for retrograde endosome to TGN transport of the receptor.
Meyer
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Zentrum für Biochemie und Molekulare Zellbiologie, Dept. Biochemie II, Universität Göttingen, Heinrich-Düker-Weg 12, D-37073 Göttingen, Germany.
Zizioli
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D
Lausmann
S
S
Eskelinen
E L
EL
Hamann
J
J
Saftig
P
P
von Figura
K
K
Schu
P
P
D033961:Adaptor Protein Complex 1; D033965:Adaptor Protein Complex alpha Subunits; D033983:Adaptor Protein Complex mu Subunits; D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D001692:Biological Transport; D002966:Clathrin / Q000235:genetics / Q000378:metabolism*; D005314:Embryonic and Fetal Development / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D017527:Receptor, IGF Type 2 / Q000235:genetics / Q000378:metabolism*
D033961:Adaptor Protein Complex 1; D033965:Adaptor Protein Complex alpha Subunits; D033983:Adaptor Protein Complex mu Subunits; D033942:Adaptor Proteins, Vesicular Transport; C499063:Ap1m1 protein, mouse; D002966:Clathrin; D008565:Membrane Proteins; D017527:Receptor, IGF Type 2; C499066:adaptor protein complex 1, mu 1 subunit