BAD regulates mammary gland morphogenesis by 4E-BP1-mediated control of localized translation in mouse and human models.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34011960.
- Also identified by DOI 10.1038/s41467-021-23269-8 and PMC identifier 8134504.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Elucidation of non-canonical protein functions can identify novel tissue homeostasis pathways. Herein, we describe a role for the Bcl-2 family member BAD in postnatal mammary gland morphogenesis. In Bad<sup>3SA</sup> knock-in mice, where BAD cannot undergo phosphorylation at 3 key serine residues, pubertal gland development is delayed due to aberrant tubulogenesis of the ductal epithelium. Proteomic and RPPA analyses identify that BAD regulates focal adhesions and the mRNA translation repressor, 4E-BP1. These results suggest that BAD modulates localized translation that drives focal adhesion maturation and cell motility. Consistent with this, cells within Bad<sup>3SA</sup> organoids contain unstable protrusions with decreased compartmentalized mRNA translation and focal adhesions, and exhibit reduced cell migration and tubulogenesis. Critically, protrusion stability is rescued by 4E-BP1 depletion. Together our results confirm an unexpected role of BAD in controlling localized translation and cell migration during mammary gland development.
Medical subject headings
- Adaptor Proteins, Signal Transducing
- Cell Cycle Proteins
- Mammary Glands, Animal
- Mammary Glands, Human
- bcl-Associated Death Protein