PT - JOURNAL ARTICLE AU - Skokan, Taylor D. AU - Hobmayer, Bert AU - McKinley, Kara L. AU - Vale, Ronald D. TI - Mechanical stretch regulates macropinocytosis in <em>Hydra vulgaris</em> AID - 10.1101/2021.12.03.471193 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.12.03.471193 4099 - http://biorxiv.org/content/early/2021/12/04/2021.12.03.471193.short 4100 - http://biorxiv.org/content/early/2021/12/04/2021.12.03.471193.full AB - Cells rely on a diverse array of engulfment processes to sense, exploit, and adapt to their environments. Macropinocytosis is a versatile example of such a process, allowing for the indiscriminate and rapid uptake of large volumes of fluid and membrane. Much of the molecular machinery essential for macropinocytosis has been well established. However, most of these studies relied on tissue culture models, leaving the regulation of this process within the context of organs and organisms unresolved. Here, we report that large-scale macropinocytosis occurs in the outer epithelial layer of the cnidarian Hydra vulgaris. Exploiting Hydra’s relatively simple body plan, we developed approaches to visualize macropinocytosis over extended periods of time in living tissue, revealing constitutive engulfment across the entire body axis. Using pharmacological perturbations, we establish a role for stretch-activated channels, including Piezo, and downstream calcium influx in inhibiting this process. Finally, we show that the direct application of planar stretch leads to calcium influx and a corresponding inhibition of macropinocytosis. Together, our approaches provide a platform for the mechanistic dissection of constitutive macropinocytosis in physiological contexts and reveal a role for macropinocytosis in responding to membrane tension.Competing Interest StatementThe authors have declared no competing interest.