Abstract
Receptors for basement membrane (BM) proteins, including dystroglycan (DG), coordinate tissue development and function by mechanisms that are only partially defined. To further elucidate these mechanisms, we generated a conditional knockout of DG in the epithelial compartment of the mouse mammary gland. Deletion of DG caused an inhibition of mammary epithelial outgrowth and a failure of lactation. Surprisingly, loss of DG in vivo did not disrupt normal tissue architecture or BM formation, even though cultured Dag1-null epithelial cells failed to assemble laminin-111 at the cell surface. The absence of DG was, however, associated with a marked loss in activity of signal transducer and activator of transcription 5 (STAT5). Loss of DG perturbed STAT5 signaling induced by either prolactin or growth hormone. We found that DG regulates signaling by both hormones in a manner that is dependent on laminin-111 binding, but independent of the DG cytoplasmic domain, suggesting that it acts via a co-receptor mechanism reliant on DG-mediated laminin assembly. These results demonstrate a requirement for DG in the growth and function of a mammalian epithelial tissue in vivo. Moreover, we reveal a selective role for DG in the control of multiple STAT5-dependent hormone signaling pathways, with implications for numerous diseases in which DG function is compromised.
Original language | English (US) |
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Pages (from-to) | 3683-3692 |
Number of pages | 10 |
Journal | Journal of Cell Science |
Volume | 123 |
Issue number | 21 |
DOIs | |
State | Published - Nov 1 2010 |
Externally published | Yes |
Keywords
- Dystroglycan
- Epithelial
- Growth hormone
- Laminin
- Mammary
- Prolactin
- STAT5
ASJC Scopus subject areas
- Cell Biology