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

Mathew S, Palamuttam RJ, Mernaugh G, Ramalingam H, Lu Z, Zhang MZ, Ishibe S, Critchley DR, Fässler R, Pozzi A, Sanders CR, Carroll TJ, Zent R
Development. 2017 144 (22): 4148-4158

PMID: 28993400 · PMCID: PMC5719244 · DOI:10.1242/dev.149914

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.

© 2017. Published by The Company of Biologists Ltd.

MeSH Terms (16)

Adherens Junctions Amino Acid Motifs Animals Binding Sites Cell Adhesion Cell Membrane Cell Polarity Gene Expression Regulation, Developmental Integrin beta1 Kidney Tubules, Collecting Mice, Inbred C57BL Morphogenesis Mutation Talin Tight Junction Proteins Ureter

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