The DOI matches its Crossref record; 80 of the 80 references it cites were found in a registry or an index.
Amiloride inhibits macropinocytosis by lowering submembranous pH and preventing Rac1 and Cdc42 signaling
Open accessAbstract
Macropinocytosis is differentiated from other types of endocytosis by its unique susceptibility to inhibitors of Na+/H+ exchange. Yet, the functional relationship between Na+/H+ exchange and macropinosome formation remains obscure. In A431 cells, stimulation by EGF simultaneously activated macropinocytosis and Na+/H+ exchange, elevating cytosolic pH and stimulating Na+ influx. Remarkably, although inhibition of Na+/H+ exchange by amiloride or HOE-694 obliterated macropinocytosis, neither cytosolic alkalinization nor Na+ influx were required. Instead, using novel probes of submembranous pH, we detected the accumulation of metabolically generated acid at sites of macropinocytosis, an effect counteracted by Na+/H+ exchange and greatly magnified when amiloride or HOE-694 were present. The acidification observed in the presence of the inhibitors did not alter receptor engagement or phosphorylation, nor did it significantly depress phosphatidylinositol-3-kinase stimulation. However, activation of the GTPases that promote actin remodelling was found to be exquisitely sensitive to the submembranous pH. This sensitivity confers to macropinocytosis its unique susceptibility to inhibitors of Na+/H+ exchange.
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Cites
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Self-citationCoordination of Rho GTPase activities during cell protrusion
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“The remodelling of the cytoskeleton that leads to macropinocytosis requires phosphatidylinositol-3-kinase (PI3K) activity at the plasma membrane (Araki et al., 1996; Rupper et al., 2001; Lindmo and Stenmark, 2006).”
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Davidson, S. M., Jonas, O., Keibler, M. A., Hou, H. W., Luengo, A., Mayers, J. R., Wyckoff, J., Del Rosario, A. M., Whitman, M., Chin, C. R., et al. (2017) · Nature Medicine · doi:10.1038/nm.4256 · Cited by 331
Metadata
- Authors
- Koivusalo, M., Welch, C., Hayashi, H., Scott, C. C., Kim, M., Alexander, T., Touret, N., Hahn, K. M., & Grinstein, S.
- Venue
- Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2010-02-15
- Volume
- 188
- Issue
- 4
- Pages
- 547-563
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- OpenAlex
- W2172260616
- Cited by
- 889
- References
- 80
- FWCI
- 12.53
- Type
- journal article
- Language
- en
- Open access
- green
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- Koivusalo, M., Welch, C., Hayashi, H., Scott, C. C., Kim, M., Alexander, T., Touret, N., Hahn, K. M., & Grinstein, S. (2010). Amiloride inhibits macropinocytosis by lowering submembranous pH and preventing Rac1 and Cdc42 signaling. Journal of Cell Biology. https://doi.org/10.1083/jcb.200908086
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