| Title: | Essential role of cyclin-G-associated kinase (Auxilin-2) in developing and mature mice |
| Author(s): | Lee DW; Zhao X; Yim YI; Eisenberg E; Greene LE; |
| Address: | "Laboratory of Cell Biology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-0301, USA" |
| ISSN/ISBN: | 1939-4586 (Electronic) 1059-1524 (Print) 1059-1524 (Linking) |
| Abstract: | "Hsc70 with its cochaperone, either auxilin or GAK, not only uncoats clathrin-coated vesicles but also acts as a chaperone during clathrin-mediated endocytosis. However, because synaptojanin is also involved in uncoating, it is not clear whether GAK is an essential gene. To answer this question, GAK conditional knockout mice were generated and then mated to mice expressing Cre recombinase under the control of the nestin, albumin, or keratin-14 promoters, all of which turn on during embryonic development. Deletion of GAK from brain, liver, or skin dramatically altered the histology of these tissues, causing the mice to die shortly after birth. Furthermore, by expressing a tamoxifen-inducible promoter to express Cre recombinase we showed that deletion of GAK caused lethality in adult mice. Mouse embryonic fibroblasts in which the GAK was disrupted showed a lack of clathrin-coated pits and a complete block in clathrin-mediated endocytosis. We conclude that GAK deletion blocks development and causes lethality in adult animals by disrupting clathrin-mediated endocytosis" |
| Keywords: | "Animals Auxilins/metabolism/*physiology Clathrin/chemistry Cyclin G Cyclin G1 Cyclins/*chemistry Embryonic Stem Cells/cytology Endocytosis Female Gene Deletion *Gene Expression Regulation, Developmental Male Mice Mice, Inbred C57BL Mice, Knockout Models, ;" |
| Notes: | "MedlineLee, Dong-Won Zhao, Xiaohong Yim, Yang-In Eisenberg, Evan Greene, Lois E eng 2008/04/25 Mol Biol Cell. 2008 Jul; 19(7):2766-76. doi: 10.1091/mbc.e07-11-1115. Epub 2008 Apr 23" |
