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Automated Imaging and Analysis for the Quantification of Fluorescently Labeled Macropinosomes
Published on: August 24, 2021
Piezo1 activation using Yoda1 inhibits macropinocytosis in A431 human epidermoid carcinoma cells
Masashi Kuriyama1, Hisaaki Hirose2, Toshihiro Masuda1
1Institute for Chemical Research, Kyoto University, Uji, Kyoto, 611-0011, Japan.
Abstract:
Macropinocytosis is a type of endocytosis accompanied by actin rearrangement-driven membrane deformation, such as lamellipodia formation and membrane ruffling, followed by the formation of large vesicles, macropinosomes. Ras-transformed cancer cells efficiently acquire exogenous amino acids for their survival through macropinocytosis. Thus, inhibition of macropinocytosis is a promising strategy for cancer therapy. To date, few specific agents that inhibit macropinocytosis have been developed. Here, focusing on the mechanosensitive ion channel Piezo1, we found that Yoda1, a Piezo1 agonist, potently inhibits macropinocytosis induced by epidermal growth factor (EGF). The inhibition of ruffle formation by Yoda1 was dependent on the extracellular Ca2+ influx through Piezo1 and on the activation of the calcium-activated potassium channel KCa3.1. This suggests that Ca2+ ions can regulate EGF-stimulated macropinocytosis. We propose the potential for macropinocytosis inhibition through the regulation of a mechanosensitive channel activity using chemical tools.
Insights
Yoda1, a Piezo1 agonist, inhibits macropinocytosis in Ras-transformed cancer cells by blocking membrane ruffling. This novel approach targets calcium influx and potassium channels, offering a potential cancer therapy strategy.
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Research
Background:
- Macropinocytosis is crucial for Ras-transformed cancer cells to acquire amino acids for survival.
- Inhibiting macropinocytosis presents a promising therapeutic strategy for cancer treatment.
- Specific inhibitors for macropinocytosis are currently limited.
Purpose of the Study:
- To investigate the role of the mechanosensitive ion channel Piezo1 in regulating macropinocytosis.
- To explore Yoda1, a Piezo1 agonist, as a potential inhibitor of cancer cell macropinocytosis.
Main Methods:
- Utilized Yoda1, a Piezo1 agonist, to study its effect on epidermal growth factor (EGF)-induced macropinocytosis.
- Investigated the dependence of Yoda1's inhibitory effect on extracellular calcium (Ca2+) influx via Piezo1.
- Examined the involvement of the calcium-activated potassium channel KCa3.1 in the observed inhibition.
Main Results:
- Yoda1 potently inhibited EGF-induced macropinocytosis.
- The inhibition of membrane ruffling by Yoda1 was dependent on extracellular Ca2+ influx through Piezo1.
- Yoda1's effect involved the activation of the KCa3.1 channel, indicating Ca2+ regulation of macropinocytosis.
Conclusions:
- Chemical modulation of mechanosensitive channels, like Piezo1, can inhibit macropinocytosis.
- This study highlights a novel mechanism for regulating macropinocytosis via ion channel activity.
- Targeting Piezo1 and associated ion channels offers a potential new avenue for cancer therapy.
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