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

Sijo Mathew, Riya J. Palamuttam, Glenda Mernaugh, Harini Ramalingam, Zhenwei Lu, Ming Zhi Zhang, Shuta Ishibe, David R. Critchley, Reinhard Fässler, Ambra Pozzi, Charles R. Sanders, Thomas J. Carroll, Roy Zent

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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 systemexpress the β1 subunit. The β1 cytoplasmic tail has two NPxYmotifs 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.

Original languageEnglish (US)
Pages (from-to)4148-4158
Number of pages11
JournalDevelopment (Cambridge)
Volume144
Issue number22
DOIs
StatePublished - Nov 15 2017

Keywords

  • Kidney
  • Nuclear magnetic resonance
  • Signaling
  • Tubules

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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