Premium
μ1A‐adaptin‐deficient mice: lethality, loss of AP‐1 binding and rerouting of mannose 6‐phosphate receptors
Author(s) -
Meyer Christoph,
Zizioli Daniela,
Lausmann Susanne,
Eskelinen EevaLiisa,
Hamann Jens,
Saftig Paul,
von Figura Kurt,
Schu Peter
Publication year - 2000
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/19.10.2193
Subject(s) - endosome , mannose 6 phosphate , biology , mannose , clathrin , microbiology and biotechnology , receptor , vesicle , golgi apparatus , mannose 6 phosphate receptor , endocytosis , biochemistry , lysosome , membrane , endoplasmic reticulum , growth factor , enzyme
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 μ1A‐adaptin gene causes embryonic lethality at day 13.5. In cells deficient in μ1A‐adaptin the remaining AP‐1 adaptins do not bind to the TGN. Polarized epithelial cells are the only cells of μ1A‐adaptin‐deficient embryos that show γ‐adaptin binding to membranes, indicating the formation of an epithelial specific AP‐1B complex and demonstrating the absence of additional μ1A 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 μ1A‐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.