Clathrin adaptor AP-2 is essential for early embryonal development.
The heterotetrameric adaptor protein (AP) complexes AP-1, AP-2, AP-3, and AP-4 play key roles in transport vesicle formation and cargo sorting in post-Golgi trafficking pathways. Studies on cultured mammalian cells have shown that AP-2 mediates rapid endocytosis of a subset of plasma membrane receptors. To determine whether this function is essential in the context of a whole mammalian organism, we carried out targeted disruption of the gene encoding the mu2 subunit of AP-2 in the mouse. We found that mu2 heterozygous mutant mice were viable and had an apparently normal phenotype. In contrast, no mu2 homozygous mutant embryos were identified among blastocysts from intercrossed heterozygotes, indicating that mu2-deficient embryos die before day 3.5 postcoitus (E3.5). These results indicate that AP-2 is indispensable for early embryonic development, which might be due to its requirement for cell viability.
Mitsunari
Takashi
T
Laboratory for Epithelial Immunobiology, Research Center for Allergy and Immunology, RIKEN, 1-7-22 Suehiro, Tsurumi, Yokohama, Kanagawa 230-0045, Japan.
Nakatsu
Fubito
F
Shioda
Noriko
N
Love
Paul E
PE
Grinberg
Alexander
A
Bonifacino
Juan S
JS
Ohno
Hiroshi
H
D033962:Adaptor Protein Complex 2 / Q000235:genetics / Q000378:metabolism*; D033983:Adaptor Protein Complex mu Subunits / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology; D047108:Embryonic Development; D004705:Endocytosis; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D006579:Heterozygote; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
D033962:Adaptor Protein Complex 2; D033983:Adaptor Protein Complex mu Subunits; C438886:adaptor protein complex 2, mu 2 subunit