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Dual roles for the Dab2 adaptor protein in embryonic development and kidney transport
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Dual roles for the Dab2 adaptor protein in embryonic development and kidney transport
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Journal Article
Dual roles for the Dab2 adaptor protein in embryonic development and kidney transport
2002
Overview
The
Disabled‐2
(
Dab2
) gene has been proposed to act as a tumor suppressor. Cell culture studies have implicated
Dab2
in signal transduction by mitogens, TGFβ and endocytosis of lipoprotein receptors. To identify
in vivo
functions of
Dab2
, targeted mutations were made in the mouse. In the absence of
Dab2
, embryos arrest prior to gastrulation with a phenotype reminiscent of those caused by deletion of some TGFβ signal transduction molecules involved in Nodal signaling.
Dab2
is expressed in the extra‐embryonic visceral endoderm but not in the epiblast.
Dab2
could be conditionally deleted from the embryo without affecting normal development, showing that
Dab2
is required in the visceral endoderm but dispensable in the embryo proper. Conditionally mutant
Dab2
−/−
mice are overtly normal, but have reduced clathrin‐coated pits in kidney proximal tubule cells and excrete specific plasma proteins in the urine, consistent with reduced transport by a lipoprotein receptor, megalin/gp330, in the proximal tubule. This evidence indicates that
Dab2
is pleiotropic and regulates both visceral endoderm function and lipoprotein receptor trafficking
in vivo
.
Publisher
John Wiley & Sons, Ltd,Nature Publishing Group UK,Springer Nature B.V,Oxford University Press
Subject
/ Adaptor Proteins, Signal Transducing
/ Adaptor Proteins, Vesicular Transport
/ Animals
/ EMBO11
/ EMBO37
/ Embryonic and Fetal Development
/ Embryos
/ Female
/ Kidney Tubules, Proximal - metabolism
/ Kidney Tubules, Proximal - pathology
/ Kidneys
/ megalin
/ Mice
/ Nodal
/ Retinol-Binding Proteins - metabolism
