Clathrin Adaptor AP-2 is Essential for Early Embryonal Development

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2005 Oct 18

PMID 16227583

Citations 70

Authors

Takashi Mitsunari

Fubito Nakatsu

Noriko Shioda

Paul E Love

Alexander Grinberg

Juan S Bonifacino

Hiroshi Ohno

Affiliations

Soon will be listed here.

Abstract

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.

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References

Folsch H, Ohno H, Bonifacino J, Mellman I . A novel clathrin adaptor complex mediates basolateral targeting in polarized epithelial cells. Cell. 1999; 99(2):189-98. DOI: 10.1016/s0092-8674(00)81650-5. View

Zizioli D, Meyer C, Guhde G, Saftig P, von Figura K, Schu P . Early embryonic death of mice deficient in gamma-adaptin. J Biol Chem. 1999; 274(9):5385-90. DOI: 10.1074/jbc.274.9.5385. View

Meyer C, Zizioli D, Lausmann S, Eskelinen E, Hamann J, Saftig P . mu1A-adaptin-deficient mice: lethality, loss of AP-1 binding and rerouting of mannose 6-phosphate receptors. EMBO J. 2000; 19(10):2193-203. PMC: 384363. DOI: 10.1093/emboj/19.10.2193. View

Nesterov A, Carter R, Sorkina T, Gill G, Sorkin A . Inhibition of the receptor-binding function of clathrin adaptor protein AP-2 by dominant-negative mutant mu2 subunit and its effects on endocytosis. EMBO J. 1999; 18(9):2489-99. PMC: 1171331. DOI: 10.1093/emboj/18.9.2489. View

Ohno H, Tomemori T, Nakatsu F, Okazaki Y, Aguilar R, Foelsch H . Mu1B, a novel adaptor medium chain expressed in polarized epithelial cells. FEBS Lett. 1999; 449(2-3):215-20. DOI: 10.1016/s0014-5793(99)00432-9. View

Bonifacino J, DellAngelica E . Molecular bases for the recognition of tyrosine-based sorting signals. J Cell Biol. 1999; 145(5):923-6. PMC: 2133128. DOI: 10.1083/jcb.145.5.923. View

Owen D, Vallis Y, Noble M, Hunter J, Dafforn T, Evans P . A structural explanation for the binding of multiple ligands by the alpha-adaptin appendage domain. Cell. 1999; 97(6):805-15. DOI: 10.1016/s0092-8674(00)80791-6. View

Gaidarov I, Keen J . Phosphoinositide-AP-2 interactions required for targeting to plasma membrane clathrin-coated pits. J Cell Biol. 1999; 146(4):755-64. PMC: 2156139. DOI: 10.1083/jcb.146.4.755. View

Ihrke G, Kyttala A, Russell M, Rous B, Luzio J . Differential use of two AP-3-mediated pathways by lysosomal membrane proteins. Traffic. 2004; 5(12):946-62. DOI: 10.1111/j.1600-0854.2004.00236.x. View

10.

Rodriguez-Boulan E, Kreitzer G, Musch A . Organization of vesicular trafficking in epithelia. Nat Rev Mol Cell Biol. 2005; 6(3):233-47. DOI: 10.1038/nrm1593. View

11.

Wang L, Magdaleno S, Tabas I, Jackowski S . Early embryonic lethality in mice with targeted deletion of the CTP:phosphocholine cytidylyltransferase alpha gene (Pcyt1a). Mol Cell Biol. 2005; 25(8):3357-63. PMC: 1069620. DOI: 10.1128/MCB.25.8.3357-3363.2005. View

12.

Moskowitz H, Yokoyama C, Ryan T . Highly cooperative control of endocytosis by clathrin. Mol Biol Cell. 2005; 16(4):1769-76. PMC: 1073659. DOI: 10.1091/mbc.e04-08-0739. View

13.

Honing S, Ricotta D, Krauss M, Spate K, Spolaore B, Motley A . Phosphatidylinositol-(4,5)-bisphosphate regulates sorting signal recognition by the clathrin-associated adaptor complex AP2. Mol Cell. 2005; 18(5):519-31. DOI: 10.1016/j.molcel.2005.04.019. View

14.

McCormick P, Martina J, Bonifacino J . Involvement of clathrin and AP-2 in the trafficking of MHC class II molecules to antigen-processing compartments. Proc Natl Acad Sci U S A. 2005; 102(22):7910-5. PMC: 1138261. DOI: 10.1073/pnas.0502206102. View

15.

Janvier K, Bonifacino J . Role of the endocytic machinery in the sorting of lysosome-associated membrane proteins. Mol Biol Cell. 2005; 16(9):4231-42. PMC: 1196333. DOI: 10.1091/mbc.e05-03-0213. View

16.

Shim J, Lee J . Molecular genetic analysis of apm-2 and aps-2, genes encoding the medium and small chains of the AP-2 clathrin-associated protein complex in the nematode Caenorhabditis elegans. Mol Cells. 2000; 10(3):309-16. View

17.

Slepnev V, De Camilli P . Accessory factors in clathrin-dependent synaptic vesicle endocytosis. Nat Rev Neurosci. 2001; 1(3):161-72. DOI: 10.1038/35044540. View

18.

Brodsky F, Chen C, Knuehl C, Towler M, Wakeham D . Biological basket weaving: formation and function of clathrin-coated vesicles. Annu Rev Cell Dev Biol. 2001; 17:517-68. DOI: 10.1146/annurev.cellbio.17.1.517. View

19.

Meyer C, Eskelinen E, Guruprasad M, von Figura K, Schu P . Mu 1A deficiency induces a profound increase in MPR300/IGF-II receptor internalization rate. J Cell Sci. 2002; 114(Pt 24):4469-76. DOI: 10.1242/jcs.114.24.4469. View

20.

Nishimura K, Nakatsu F, Kashiwagi K, Ohno H, Saito T, Igarashi K . Essential role of S-adenosylmethionine decarboxylase in mouse embryonic development. Genes Cells. 2002; 7(1):41-7. DOI: 10.1046/j.1356-9597.2001.00494.x. View