期刊
JOURNAL OF CELL BIOLOGY
卷 196, 期 6, 页码 789-800出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201105101
关键词
-
类别
资金
- National Institutes of Health [IDDRC P30HD40677]
- March of Dimes
- Spina Bifida Association
- National Institute of Child Health and Human Development [NICHD-R01-HD058629]
Hectd 1 mutant mouse embryos exhibit the neural tube defect exencephaly associated with abnormal cranial mesenchyme. Cellular rearrangements in cranial mesenchyme are essential during neurulation for elevation of the neural folds. Here we investigate the molecular basis of the abnormal behavior of Hectd 1 mutant cranial mesenchyme. We demonstrate that Hectd 1 is a functional ubiquitin ligase and that one of its substrates is Hsp90, a chaperone protein with both intra- and extracellular clients. Extracellular Hsp90 enhances migration of multiple cell types. In mutant cranial mesenchyme cells, both secretion of Hsp90 and emigration of cells from cranial mesenchyme explants were enhanced. Importantly, we show that this enhanced emigration was highly dependent on the excess Hsp90 secreted from mutant cells. Together, our data set forth a model whereby increased secretion of Hsp90 in the cranial mesenchyme of Hectd 1 mutants is responsible, at least in part, for the altered organization and behavior of these cells and provides a potential molecular mechanism underlying the neural tube defect.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据