Mechanosensing is a vital cellular process, but how cells transduce mechanical stimuli is not well defined. Here, Ulbricht et al. report that, in mammalian cells, tension-induced unfolding of the cytoskeleton protein filamin is sensed by BAG3, a component of the CASA (chaperone-assisted selective autophagy) complex. BAG3 binds to unfolded filamin and to the adaptor protein synaptopodin 2 (SYNPO2); SYNPO2 links the CASA complex to a membrane-tethering and fusion complex, which leads to autophagosome formation and filamin degradation. In addition, BAG3 stimulates the transcriptional activators YAP and TAZ, which leads to increased filamin mRNA and protein levels. Thus, by regulating the degradation and transcription of filamin in mechanically strained cells, BAG3 is a key transducer of mechanical signals.
ORIGINAL RESEARCH PAPER
Ulbricht, A. et al. Cellular mechanotransduction relies on tension-induced and chaperone-assisted autophagy. Curr. Biol. 23, 430–435 (2013)
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Du Toit, A. Transducing mechanical signals. Nat Rev Mol Cell Biol 14, 195 (2013). https://doi.org/10.1038/nrm3556
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DOI: https://doi.org/10.1038/nrm3556