Role of Phosphatidylinositol 3' Kinase and a Downstream Pleckstrin Homology Domain-containing Protein in Controlling Chemotaxis in Dictyostelium

doi:10.1083/jcb.153.4.795

Published online 14 May 2001. doi:10.1083/jcb.153.4.795

This Article

	Full Text
	PDF (Full Text)
	PPT slides of all figures
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JCB
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Funamoto, S.
	Articles by Firtel, R. A.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Funamoto, S.
	Articles by Firtel, R. A.


Social Bookmarking

	What's this?

© The Rockefeller University Press, 0021-9525/2001/5/795/ $5.00
The Journal of Cell Biology, Volume 153, Number 4, May 14, 2001 795-810

Original Article

Role of Phosphatidylinositol 3' Kinase and a Downstream Pleckstrin Homology Domain–containing Protein in Controlling Chemotaxis in Dictyostelium

Satoru Funamoto^a, Kristina Milan^a, Ruedi Meili^a, and Richard A. Firtel^a
^a Section of Cell and Developmental Biology and Center for Molecular Genetics, University of California at San Diego, La Jolla, California 92093

Correspondence to: Richard A. Firtel, Center for Molecular Genetics, Rm. 225, University of California at San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0634. Tel:(858) 534-2788 Fax:(858) 534-7073 E-mail:rafirtel{at}ucsd.edu.

We show that cells lacking two Dictyostelium class I phosphatidylinositol(PI) 3' kinases (PI3K and pi3k1/2-null cells) or wild-type cellstreated with the PI3K inhibitor LY294002 are unable to properlypolarize, are very defective in the temporal, spatial, and quantitativeregulation of chemoattractant-mediated filamentous (F)-actinpolymerization, and chemotax very slowly. PI3K is thought toproduce membrane lipid-binding sites for localization of PHdomain–containing proteins. We demonstrate that in responseto chemoattractants three PH domain–containing proteinsdo not localize to the leading edge in pi3k1/2-null cells, andthe translocation is blocked in wild-type cells by LY294002.Cells lacking one of these proteins, phdA-null cells, exhibitdefects in the level and kinetics of actin polymerization atthe leading edge and have chemotaxis phenotypes that are distinctfrom those described previously for protein kinase B (PKB) (pkbA)-nullcells. Phenotypes of PhdA-dominant interfering mutations suggestthat PhdA is an adaptor protein that regulates F-actin localizationin response to chemoattractants and links PI3K to the controlof F-actin polymerization at the leading edge during pseudopodformation. We suggest that PKB and PhdA lie downstream fromPI3K and control different downstream effector pathways thatare essential for proper chemotaxis.

Key Words: Dictyostelium, PH domain, actin polymerization, chemotaxis,PI3 kinase

Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?

This article has been cited by other articles:

Tang, Y., Gomer, R. H. (2008). A Protein with Similarity to PTEN Regulates Aggregation Territory Size by Decreasing Cyclic AMP Pulse Size during Dictyostelium discoideum Development. Eukaryot Cell 7: 1758-1770 [Abstract] [Full Text]
Osawa, S., Funamoto, S., Nobuhara, M., Wada-Kakuda, S., Shimojo, M., Yagishita, S., Ihara, Y. (2008). Phosphoinositides Suppress {gamma}-Secretase in Both the Detergent-soluble and -insoluble States. J. Biol. Chem. 283: 19283-19292 [Abstract] [Full Text]
Bolourani, P., Spiegelman, G. B., Weeks, G. (2008). Rap1 Activation in Response to cAMP Occurs Downstream of Ras Activation during Dictyostelium Aggregation. J. Biol. Chem. 283: 10232-10240 [Abstract] [Full Text]
Heath, R. J. W., Insall, R. H. (2008). Dictyostelium MEGAPs: F-BAR domain proteins that regulate motility and membrane tubulation in contractile vacuoles. J. Cell Sci. 121: 1054-1064 [Abstract] [Full Text]
Kolsch, V., Charest, P. G., Firtel, R. A. (2008). The regulation of cell motility and chemotaxis by phospholipid signaling. J. Cell Sci. 121: 551-559 [Abstract] [Full Text]
Veltman, D. M., Keizer-Gunnik, I., Van Haastert, P. J.M. (2008). Four key signaling pathways mediating chemotaxis in Dictyostelium discoideum. J. Cell Biol. 180: 747-753 [Abstract] [Full Text]
Jeon, T. J., Lee, D.-J., Lee, S., Weeks, G., Firtel, R. A. (2007). Regulation of Rap1 activity by RapGAP1 controls cell adhesion at the front of chemotaxing cells. J. Cell Biol. 179: 833-843 [Abstract] [Full Text]
Kortholt, A., King, J. S., Keizer-Gunnink, I., Harwood, A. J., Van Haastert, P. J.M. (2007). Phospholipase C Regulation of Phosphatidylinositol 3,4,5-trisphosphate-mediated Chemotaxis. Mol. Biol. Cell 18: 4772-4779 [Abstract] [Full Text]
Evans, J. H., Falke, J. J. (2007). Ca2+ influx is an essential component of the positive-feedback loop that maintains leading-edge structure and activity in macrophages. Proc. Natl. Acad. Sci. USA 104: 16176-16181 [Abstract] [Full Text]
Xu, X., Meier-Schellersheim, M., Yan, J., Jin, T. (2007). Locally controlled inhibitory mechanisms are involved in eukaryotic GPCR-mediated chemosensing. J. Cell Biol. 178: 141-153 [Abstract] [Full Text]
Chen, Y., McQuade, K. J., Guan, X.-J., Thomason, P. A., Wert, M. S., Stock, J. B., Cox, E. C. (2007). Isoprenylcysteine Carboxy Methylation Is Essential for Development in Dictyostelium discoideum. Mol. Biol. Cell 18: 4106-4118 [Abstract] [Full Text]
Basu, S., Ray, N. T., Atkinson, S. J., Broxmeyer, H. E. (2007). Protein Phosphatase 2A Plays an Important Role in Stromal Cell-Derived Factor-1/CXC Chemokine Ligand 12-Mediated Migration and Adhesion of CD34+ Cells. J. Immunol. 179: 3075-3085 [Abstract] [Full Text]
Wessels, D., Lusche, D. F., Kuhl, S., Heid, P., Soll, D. R. (2007). PTEN plays a role in the suppression of lateral pseudopod formation during Dictyostelium motility and chemotaxis. J. Cell Sci. 120: 2517-2531 [Abstract] [Full Text]
Sasaki, A. T., Janetopoulos, C., Lee, S., Charest, P. G., Takeda, K., Sundheimer, L. W., Meili, R., Devreotes, P. N., Firtel, R. A. (2007). G protein-independent Ras/PI3K/F-actin circuit regulates basic cell motility. J. Cell Biol. 178: 185-191 [Abstract] [Full Text]
van Haastert, P. J.M., Keizer-Gunnink, I., Kortholt, A. (2007). Essential role of PI3-kinase and phospholipase A2 in Dictyostelium discoideum chemotaxis. J. Cell Biol. 177: 809-816 [Abstract] [Full Text]
Xu, X., Muller-Taubenberger, A., Adley, K. E., Pawolleck, N., Lee, V. W. Y., Wiedemann, C., Sihra, T. S., Maniak, M., Jin, T., Williams, R. S. B. (2007). Attenuation of Phospholipid Signaling Provides a Novel Mechanism for the Action of Valproic Acid. Eukaryot Cell 6: 899-906 [Abstract] [Full Text]
Keizer-Gunnink, I., Kortholt, A., Van Haastert, P. J.M. (2007). Chemoattractants and chemorepellents act by inducing opposite polarity in phospholipase C and PI3-kinase signaling. J. Cell Biol. 177: 579-585 [Abstract] [Full Text]
Asperti-Boursin, F., Real, E., Bismuth, G., Trautmann, A., Donnadieu, E. (2007). CCR7 ligands control basal T cell motility within lymph node slices in a phosphoinositide 3-kinase- independent manner. J. Exp. Med. 204: 1167-1179 [Abstract] [Full Text]
Takeda, K., Sasaki, A. T., Ha, H., Seung, H.-A, Firtel, R. A. (2007). Role of Phosphatidylinositol 3-Kinases in Chemotaxis in Dictyostelium. J. Biol. Chem. 282: 11874-11884 [Abstract] [Full Text]
Han, J. W., Leeper, L., Rivero, F., Chung, C. Y. (2006). Role of RacC for the Regulation of WASP and Phosphatidylinositol 3-Kinase during Chemotaxis of Dictyostelium. J. Biol. Chem. 281: 35224-35234 [Abstract] [Full Text]
Bolourani, P., Spiegelman, G. B., Weeks, G. (2006). Delineation of the Roles Played by RasG and RasC in cAMP-dependent Signal Transduction during the Early Development of Dictyostelium discoideum. Mol. Biol. Cell 17: 4543-4550 [Abstract] [Full Text]
Sakakibara, A., Horwitz, A. F. (2006). Mechanism of polarized protrusion formation on neuronal precursors migrating in the developing chicken cerebellum. J. Cell Sci. 119: 3583-3592 [Abstract] [Full Text]
Veltman, D. M., Van Haastert, P. J.M. (2006). Guanylyl Cyclase Protein and cGMP Product Independently Control Front and Back of Chemotaxing Dictyostelium Cells. Mol. Biol. Cell 17: 3921-3929 [Abstract] [Full Text]
Samadani, A., Mettetal, J., van Oudenaarden, A. (2006). Cellular asymmetry and individuality in directional sensing. Proc. Natl. Acad. Sci. USA 103: 11549-11554 [Abstract] [Full Text]
Wood, W., Faria, C., Jacinto, A. (2006). Distinct mechanisms regulate hemocyte chemotaxis during development and wound healing in Drosophila melanogaster. J. Cell Biol. 173: 405-416 [Abstract] [Full Text]
Loovers, H. M., Postma, M., Keizer-Gunnink, I., Huang, Y. E., Devreotes, P. N., van Haastert, P. J.M. (2006). Distinct Roles of PI(3,4,5)P3 during Chemoattractant Signaling in Dictyostelium: A Quantitative In Vivo Analysis by Inhibition of PI3-Kinase. Mol. Biol. Cell 17: 1503-1513 [Abstract] [Full Text]
Wessels, D., Srikantha, T., Yi, S., Kuhl, S., Aravind, L., Soll, D. R. (2006). The Shwachman-Bodian-Diamond syndrome gene encodes an RNA-binding protein that localizes to the pseudopod of Dictyostelium amoebae during chemotaxis. J. Cell Sci. 119: 370-379 [Abstract] [Full Text]
Comer, F. I., Parent, C. A. (2006). Phosphoinositide 3-Kinase Activity Controls the Chemoattractant-mediated Activation and Adaptation of Adenylyl Cyclase. Mol. Biol. Cell 17: 357-366 [Abstract] [Full Text]
Lee, S., Comer, F. I., Sasaki, A., McLeod, I. X., Duong, Y., Okumura, K., Yates, J. R. III, Parent, C. A., Firtel, R. A. (2005). TOR Complex 2 Integrates Cell Movement during Chemotaxis and Signal Relay in Dictyostelium. Mol. Biol. Cell 16: 4572-4583 [Abstract] [Full Text]
Mendoza, M. C., Du, F., Iranfar, N., Tang, N., Ma, H., Loomis, W. F., Firtel, R. A. (2005). Loss of SMEK, a Novel, Conserved Protein, Suppresses mek1 Null Cell Polarity, Chemotaxis, and Gene Expression Defects. Mol. Cell. Biol. 25: 7839-7853 [Abstract] [Full Text]
Myers, S. A., Han, J. W., Lee, Y., Firtel, R. A., Chung, C. Y. (2005). A Dictyostelium Homologue of WASP Is Required for Polarized F-Actin Assembly during Chemotaxis. Mol. Biol. Cell 16: 2191-2206 [Abstract] [Full Text]
Patel, H., Barber, D. L. (2005). A developmentally regulated Na-H exchanger in Dictyostelium discoideum is necessary for cell polarity during chemotaxis. J. Cell Biol. 169: 321-329 [Abstract] [Full Text]
Xu, X., Meier-Schellersheim, M., Jiao, X., Nelson, L. E., Jin, T. (2005). Quantitative Imaging of Single Live Cells Reveals Spatiotemporal Dynamics of Multistep Signaling Events of Chemoattractant Gradient Sensing in Dictyostelium. Mol. Biol. Cell 16: 676-688 [Abstract] [Full Text]
Marchetti, A., Mercanti, V., Cornillon, S., Alibaud, L., Charette, S. J., Cosson, P. (2004). Formation of multivesicular endosomes in Dictyostelium. J. Cell Sci. 117: 6053-6059 [Abstract] [Full Text]
Ma, L., Janetopoulos, C., Yang, L., Devreotes, P. N., Iglesias, P. A. (2004). Two Complementary, Local Excitation, Global Inhibition Mechanisms Acting in Parallel Can Explain the Chemoattractant-Induced Regulation of PI(3,4,5)P3 Response in Dictyostelium Cells. Biophys. J 87: 3764-3774 [Abstract] [Full Text]
Lee, S., Rivero, F., Park, K. C., Huang, E., Funamoto, S., Firtel, R. A. (2004). Dictyostelium PAKc Is Required for Proper Chemotaxis. Mol. Biol. Cell 15: 5456-5469 [Abstract] [Full Text]
Sun, C. X., Downey, G. P., Zhu, F., Koh, A. L. Y., Thang, H., Glogauer, M. (2004). Rac1 is the small GTPase responsible for regulating the neutrophil chemotaxis compass. Blood 104: 3758-3765 [Abstract] [Full Text]
Sasaki, A. T., Chun, C., Takeda, K., Firtel, R. A. (2004). Localized Ras signaling at the leading edge regulates PI3K, cell polarity, and directional cell movement. J. Cell Biol. 167: 505-518 [Abstract] [Full Text]
Franca-Koh, J., Devreotes, P. N. (2004). Moving Forward: Mechanisms of Chemoattractant Gradient Sensing. Physiology 19: 300-308 [Abstract] [Full Text]
Gao, T., Knecht, D., Tang, L., Hatton, R. D., Gomer, R. H. (2004). A Cell Number Counting Factor Regulates Akt/Protein Kinase B To Regulate Dictyostelium discoideum Group Size. Eukaryot Cell 3: 1176-1184 [Abstract] [Full Text]
Postma, M., Roelofs, J., Goedhart, J., Loovers, H. M., Visser, A. J. W. G., Van Haastert, P. J. M. (2004). Sensitization of Dictyostelium chemotaxis by phosphoinositide-3-kinase-mediated self-organizing signalling patches. J. Cell Sci. 117: 2925-2935 [Abstract] [Full Text]
Wessels, D., Brincks, R., Kuhl, S., Stepanovic, V., Daniels, K. J., Weeks, G., Lim, C. J., Spiegelman, G., Fuller, D., Iranfar, N., Loomis, W. F., Soll, D. R. (2004). RasC Plays a Role in Transduction of Temporal Gradient Information in the Cyclic-AMP Wave of Dictyostelium discoideum. Eukaryot Cell 3: 646-662 [Abstract] [Full Text]
Postma, M., Roelofs, J., Goedhart, J., Gadella, T. W.J., Visser, A. J.W.G., Van Haastert, P. J.M. (2003). Uniform cAMP Stimulation of Dictyostelium Cells Induces Localized Patches of Signal Transduction and Pseudopodia. Mol. Biol. Cell 14: 5019-5027 [Abstract] [Full Text]
Chen, L., Janetopoulos, C., Huang, Y. E., Iijima, M., Borleis, J., Devreotes, P. N. (2003). Two Phases of Actin Polymerization Display Different Dependencies on PI(3,4,5)P3 Accumulation and Have Unique Roles during Chemotaxis. Mol. Biol. Cell 14: 5028-5037 [Abstract] [Full Text]
Merlot, S., Meili, R., Pagliarini, D. J., Maehama, T., Dixon, J. E., Firtel, R. A. (2003). A PTEN-related 5-Phosphatidylinositol Phosphatase Localized in the Golgi. J. Biol. Chem. 278: 39866-39873 [Abstract] [Full Text]
Falk, D. L., Wessels, D., Jenkins, L., Pham, T., Kuhl, S., Titus, M. A., Soll, D. R. (2003). Shared, unique and redundant functions of three members of the class I myosins (MyoA, MyoB and MyoF) in motility and chemotaxis in Dictyostelium. J. Cell Sci. 116: 3985-3999 [Abstract] [Full Text]
Merlot, S., Firtel, R. A. (2003). Leading the way: directional sensing through phosphatidylinositol 3-kinase and other signaling pathways. J. Cell Sci. 116: 3471-3478 [Abstract] [Full Text]
Atwal, J. K., Singh, K. K., Tessier-Lavigne, M., Miller, F. D., Kaplan, D. R. (2003). Semaphorin 3F Antagonizes Neurotrophin-Induced Phosphatidylinositol 3-Kinase and Mitogen-Activated Protein Kinase Kinase Signaling: A Mechanism for Growth Cone Collapse. J. Neurosci. 23: 7602-7609 [Abstract] [Full Text]
Devreotes, P., Janetopoulos, C. (2003). Eukaryotic Chemotaxis: Distinctions between Directional Sensing and Polarization. J. Biol. Chem. 278: 20445-20448 [Abstract] [Full Text]
Huang, Y. E., Iijima, M., Parent, C. A., Funamoto, S., Firtel, R. A., Devreotes, P. (2003). Receptor-mediated Regulation of PI3Ks Confines PI(3,4,5)P3 to the Leading Edge of Chemotaxing Cells. Mol. Biol. Cell 14: 1913-1922 [Abstract] [Full Text]
Sun, B., Firtel, R. A. (2003). A Regulator of G Protein Signaling-containing Kinase Is Important for Chemotaxis and Multicellular Development in Dictyostelium. Mol. Biol. Cell 14: 1727-1743 [Abstract] [Full Text]
Loovers, H. M., Veenstra, K., Snippe, H., Pesesse, X., Erneux, C., van Haastert, P. J. M. (2003). A Diverse Family of Inositol 5-Phosphatases Playing a Role in Growth and Development in Dictyostelium discoideum. J. Biol. Chem. 278: 5652-5658 [Abstract] [Full Text]
Han, Y.-H., Chung, C. Y., Wessels, D., Stephens, S., Titus, M. A., Soll, D. R., Firtel, R. A. (2002). Requirement of a Vasodilator-stimulated Phosphoprotein Family Member for Cell Adhesion, the Formation of Filopodia, and Chemotaxis in Dictyostelium. J. Biol. Chem. 277: 49877-49887 [Abstract] [Full Text]
Fox, J. A., Ung, K., Tanlimco, S. G., Jirik, F. R. (2002). Disruption of a Single Pten Allele Augments the Chemotactic Response of B Lymphocytes to Stromal Cell-Derived Factor-1. J. Immunol. 169: 49-54 [Abstract] [Full Text]
Hannigan, M., Zhan, L., Li, Z., Ai, Y., Wu, D., Huang, C.-K. (2002). Neutrophils lacking phosphoinositide 3-kinase gamma show loss of directionality during N-formyl-Met-Leu-Phe-induced chemotaxis. Proc. Natl. Acad. Sci. USA 99: 3603-3608 [Abstract] [Full Text]
Friedl, P., Borgmann, S., Brocker, E.-B. (2001). Amoeboid leukocyte crawling through extracellular matrix: lessons from the Dictyostelium paradigm of cell movement. J. Leukoc. Biol. 70: 491-509 [Abstract] [Full Text]