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Talin regulates integrin β1-dependent and -independent cell functions in ureteric bud development
Sijo Mathew1, Riya J Palamuttam1, Glenda Mernaugh1
1Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Development (Cambridge, England)
|October 11, 2017
Summary
Talin proteins are essential for kidney collecting duct development. Disrupting talin binding to integrin β1 subunits caused moderate defects, while complete talin absence led to severe kidney abnormalities.
Area of Science:
- Developmental Biology
- Cell Biology
- Molecular Biology
Background:
- Kidney collecting system development relies on cell-extracellular matrix interactions mediated by integrins.
- Integrins, heterodimeric transmembrane receptors, utilize cytoplasmic tails with NPxY motifs for signaling.
- Talins are scaffolding proteins proposed to link integrins to the actin cytoskeleton and activate integrins via the NPxY motif.
Purpose of the Study:
- To investigate the role of talin binding to the integrin β1 subunit's proximal NPxY motif in mouse kidney collecting system development.
- To elucidate the specific functions of talin in kidney development beyond its interaction with the integrin β1 NPxY motif.
Main Methods:
- Generation of mice with a selective Y-to-A mutation in the integrin β1 proximal NPxY motif.
- Analysis of kidney development and collecting duct cell functions in mutant mice.
- Conditional knockout of talins in the developing ureteric bud to assess their necessity.
Main Results:
- Mice with the Y-to-A mutation exhibited hypoplastic dysplastic kidney collecting systems.
- Collecting duct cells with the mutation showed moderate defects in adhesion, migration, proliferation, and signaling.
- Complete talin absence in the ureteric bud resulted in kidney agenesis and severe cytoskeletal, adhesion, and polarity defects in collecting duct cells.
Conclusions:
- Talin binding to the integrin β1 NPxY motif is crucial for normal kidney collecting system development.
- Talins play essential roles in kidney development that are not solely dependent on their interaction with the integrin β1 NPxY motif.
- Talins are critical for establishing cytoskeletal organization, cell adhesion, and polarity during kidney morphogenesis.
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