Actomyosin forces trigger a conformational change in desmoplakin within desmosomes
Biorxiv : the Preprint Server for Biology
|November 28, 2024
Summary
Cellular desmosomes, crucial for tissue strength, sense mechanical stress. Actomyosin forces trigger a conformational change in desmoplakin, revealing its mechanosensitive nature.
Area of Science:
- Cell Biology
- Biophysics
- Biochemistry
Background:
- Desmosomes are vital cell-cell adhesion structures enabling tissues to withstand mechanical stress.
- Dysfunctional desmosomes are linked to skin disorders and cardiomyopathies.
- The mechanism by which desmosomes sense and respond to mechanical forces remains unclear.
Purpose of the Study:
- To investigate how desmosomes sense and respond to mechanical stimuli.
- To elucidate the role of desmoplakin in mediating cellular mechanical responses.
Main Methods:
- Super-resolution imaging
- Förster resonance energy transfer (FRET)-based tension sensors
- Atomistic computer simulations
- Biochemical assays
Main Results:
- Actomyosin forces induce a conformational change in desmoplakin, a key cytoplasmic desmosomal protein.
- In MCF7 cells, actomyosin contractility reorients keratin intermediate filaments, transmitting force to desmoplakin.
- This force converts the N-terminal plakin domain of desmoplakin from a closed to an open conformation.
Conclusions:
- Desmoplakin is mechanosensitive, exhibiting a force-induced conformational change in response to cellular load.
- This study reveals a novel mechanism for mechanical force transduction in desmosomes.
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