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Talin regulates integrin β1-dependent and -independent cell functions in ureteric bud development.

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journal contribution
posted on 23.08.2019, 14:28 by S Mathew, RJ Palamuttam, G Mernaugh, H Ramalingam, Z Lu, M-Z Zhang, S Ishibe, DR Critchley, R Fässler, A Pozzi, CR Sanders, TJ Carroll, R Zent
Kidney collecting system development requires integrin-dependent cell-extracellular matrix interactions. Integrins are heterodimeric transmembrane receptors consisting of α and β subunits; crucial integrins in the kidney collecting system express the β1 subunit. The β1 cytoplasmic tail has two NPxY motifs that mediate functions by binding to cytoplasmic signaling and scaffolding molecules. Talins, scaffolding proteins that bind to the membrane proximal NPxY motif, are proposed to activate integrins and to link them to the actin cytoskeleton. We have defined the role of talin binding to the β1 proximal NPxY motif in the developing kidney collecting system in mice that selectively express a Y-to-A mutation in this motif. The mice developed a hypoplastic dysplastic collecting system. Collecting duct cells expressing this mutation had moderate abnormalities in cell adhesion, migration, proliferation and growth factor-dependent signaling. In contrast, mice lacking talins in the developing ureteric bud developed kidney agenesis and collecting duct cells had severe cytoskeletal, adhesion and polarity defects. Thus, talins are essential for kidney collecting duct development through mechanisms that extend beyond those requiring binding to the β1 integrin subunit NPxY motif.

Funding

S.M. was funded by an American Heart Association Scientist Development grant (16SDG29740001). This work was funded by U.S. Department of Veterans Affairs Merit Review Awards (1I01BX002025 to A.P. and 1I01BX002196 to R.Z.) and by the National Institute of Diabetes and Digestive and Kidney Disease (R01-DK083187, R01-DK075594 and R01-DK069221 to R.Z., R01-DK095761 to A.P., and R01- DK080004, R01-DK095057 and R01-DK106743 to T.J.C.)

History

Citation

Development, 144 (22), pp. 4148-4158

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/Biological Sciences/Molecular & Cell Biology

Version

VoR (Version of Record)

Published in

Development

Publisher

The Company of Biologists Ltd

eissn

1477-9129

Acceptance date

28/09/2017

Copyright date

2017

Available date

23/08/2019

Notes

Supplementary information available online at http://dev.biologists.org/lookup/doi/10.1242/dev.149914.supplemental

Language

en