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Talin gets SHANKed in the fight for integrin activation

Nature Cell Biology volume 19, pages 265–267 (2017)Cite this article

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Genetic mutations in the SHANK family of proteins are linked to multiple neuropsychiatric disorders including autism spectrum disorders. A study now elucidates critical roles for SHANK in regulating integrin-mediated cell–extracellular matrix adhesion, by sequestering integrin activators.

The correct regulation of the actin cytoskeleton is crucial for cellular function and, subsequently, for tissue organization. It is becoming ever more apparent that regulators of signalling to the actin cytoskeleton are disrupted in neuropsychiatric disorders1. The family of SH3 and multiple ankyrin repeat domains (SHANK) proteins are scaffold proteins located in the postsynaptic density of excitatory synapses, and are also expressed in many different tissues throughout the body2. Deletion of the SHANK3 gene results in Phelan–McDermid syndrome, predominantly leading to neurological disorders, with many other tissues also being affected3. Knockout of Shank3 in mice results in autistic-like behaviour4, which can be overcome by targeting regulators of the actin cytoskeleton, for example by inhibiting cofilin or activating Rac1 (ref. 5). Although these results suggest a link exists between Shank proteins and the regulation of the actin cytoskeleton in neuropsychological disorders, the mechanism is not clear. In this issue, Lilja et al. demonstrate a role for Shank in regulating adhesion between cells and the extracellular matrix (ECM), preventing talin recruitment and integrin activation through binding and sequestering integrin-activating GTPases6.

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Figure 1: Shank suppresses talin-mediated integrin activation and adhesion formation.

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  1. Paul Atherton and Christoph Ballestrem are at the Wellcome Trust Centre for Cell-Matrix Research, University of Manchester, Manchester M13 9PT, UK,

    Paul Atherton & Christoph Ballestrem

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  1. Paul Atherton
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Correspondence to Christoph Ballestrem.

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Atherton, P., Ballestrem, C. Talin gets SHANKed in the fight for integrin activation. Nat Cell Biol 19, 265–267 (2017). https://doi.org/10.1038/ncb3501

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