The DOI matches its Crossref record; 76 of the 76 references it cites were found in a registry or an index.
An enzymatic cascade of Rab5 effectors regulates phosphoinositide turnover in the endocytic pathway
Open accessAbstract
Generation and turnover of phosphoinositides (PIs) must be coordinated in a spatial- and temporal-restricted manner. The small GTPase Rab5 interacts with two PI 3-kinases, Vps34 and PI3Kβ, suggesting that it regulates the production of 3-PIs at various stages of the early endocytic pathway. Here, we discovered that Rab5 also interacts directly with PI 5- and PI 4-phosphatases and stimulates their activity. Rab5 regulates the production of phosphatidylinositol 3-phosphate (PtdIns[3]P) through a dual mechanism, by directly phosphorylating phosphatidylinositol via Vps34 and by a hierarchical enzymatic cascade of phosphoinositide-3-kinaseβ (PI3Kβ), PI 5-, and PI 4-phosphatases. The functional importance of such an enzymatic pathway is demonstrated by the inhibition of transferrin uptake upon silencing of PI 4-phosphatase and studies in weeble mutant mice, where deficiency of PI 4-phosphatase causes an increase of PtdIns(3,4)P2 and a reduction in PtdIns(3)P. Activation of PI 3-kinase at the plasma membrane is accompanied by the recruitment of Rab5, PI 4-, and PI 5-phosphatases to the cell cortex. Our data provide the first evidence for a dual role of a Rab GTPase in regulating both generation and turnover of PIs via PI kinases and phosphatases to coordinate signaling functions with organelle homeostasis.
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Cites
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Self-citationSARA, a FYVE Domain Protein that Recruits Smad2 to the TGFβ Receptor
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Cited by
Rab GTPases as coordinators of vesicle traffic
Stenmark, H. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2728 · Cited by 3,413
Phosphoinositides in cell regulation and membrane dynamics
Di Paolo, G., & De Camilli, P. (2006) · Nature · doi:10.1038/nature05185 · Cited by 2,790
The emerging mechanisms of isoform-specific PI3K signalling
Vanhaesebroeck, B., Guillermet-Guibert, J., Graupera, M., & Bilanges, B. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2882 · Cited by 1,767
Regulation of Mammalian Autophagy in Physiology and Pathophysiology
Ravikumar, B., Sarkar, S., Davies, J. E., Futter, M., Garcia-Arencibia, M., Green-Thompson, Z. W., Jimenez-Sanchez, M., Korolchuk, V. I., Lichtenberg, M., Luo, S., et al. (2010) · Physiological Reviews · doi:10.1152/physrev.00030.2009 · Cited by 1,727
Phosphoinositides: Tiny Lipids With Giant Impact on Cell Regulation
Balla, T. (2013) · Physiological Reviews · doi:10.1152/physrev.00028.2012 · Cited by 1,638
Metadata
- Authors
- Shin, H.-W., Hayashi, M., Christoforidis, S., Lacas-Gervais, S., Hoepfner, S., Wenk, M. R., Modregger, J., Uttenweiler-Joseph, S., Wilm, M., Nystuen, A., Frankel, W. N., Solimena, M., De Camilli, P., & Zerial, M.
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2005-08-15
- Volume
- 170
- Issue
- 4
- Pages
- 607-618
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- OpenAlex
- W2110491903
- Cited by
- 397
- References
- 76
- FWCI
- 8.78
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Shin, H.-W., Hayashi, M., Christoforidis, S., Lacas-Gervais, S., Hoepfner, S., Wenk, M. R., Modregger, J., Uttenweiler-Joseph, S., Wilm, M., Nystuen, A., Frankel, W. N., Solimena, M., De Camilli, P., & Zerial, M. (2005). An enzymatic cascade of Rab5 effectors regulates phosphoinositide turnover in the endocytic pathway. The Journal of Cell Biology. https://doi.org/10.1083/jcb.200505128
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