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.
journal_name
Mol Biol Celljournal_title
Molecular biology of the cellauthors
Lee DW,Zhao X,Yim YI,Eisenberg E,Greene LEdoi
10.1091/mbc.e07-11-1115subject
Has Abstractpub_date
2008-07-01 00:00:00pages
2766-76issue
7eissn
1059-1524issn
1939-4586pii
E07-11-1115journal_volume
19pub_type
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