Journal Article FZJ-2021-03367

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Strain induced mechanoresponse depends on cell contractility and BAG3-mediated autophagy

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2021
American Society for Cell Biology Bethesda, Md.

Molecular biology of the cell 32(20), () [10.1091/mbc.E21-05-0254]

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Abstract: Basically, all mammalian tissues are constantly exposed to a variety of environmental mechanical signals. Depending on the signal strength, mechanics intervenes in a multitude of cellular processes and is thus capable of inducing simple cellular adaptations but also complex differentiation processes and even apoptosis. The underlying recognition typically depends on mechanosensitive proteins, which most often sense the mechanical signal for the induction of a cellular signaling cascade by changing their protein conformation. However, the fate of mechanosensors after mechanical stress application is still poorly understood, and it remains unclear whether protein degradation pathways affect the mechanosensitivity of cells. Here, we show that cyclic stretch induces autophagosome formation in a time-dependent manner. Formation depends on the cochaperone BAG family molecular chaperone regulator 3 (BAG3) and thus likely involves BAG3-mediated chaperone-assisted selective autophagy. Furthermore, we demonstrate that strain-induced cell reorientation is clearly delayed upon inhibition of autophagy, suggesting a bidirectional cross-talk between mechanotransduction and autophagic degradation. The strength of the observed delay depends on stable adhesion structures and stress fiber formation in a Ras homologue family member A (RhoA)-dependent manner.

Classification:

Contributing Institute(s):
  1. Mechanobiologie (IBI-2)
Research Program(s):
  1. 5241 - Molecular Information Processing in Cellular Systems (POF4-524) (POF4-524)
  2. DFG project 388932620 - FOR 2743: Zelluläre Schutzmechanismen gegen mechanischen Stress (388932620)

Appears in the scientific report 2021
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Medline ; OpenAccess ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Essential Science Indicators ; IF < 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection
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Open Access

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