A<i>Dictyostelium</i>Homologue of WASP Is Required for Polarized F-Actin Assembly during Chemotaxis

Myers, Scott A.; Han, Ji Yun; Lee, Yoonsung; Firtel, Richard A.; Chung, Chang Y.

doi:10.1091/mbc.e04-09-0844

Cited by 74 publications

(70 citation statements)

References 73 publications

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“…Activated Rac1 proteins interact with numerous proteins implicated in the regulation of actin dynamics and at least a half dozen have been detected in Dictyostelium so far: multiple IQGAP-related proteins, e.g., DGAP1 36 and GAPA, 37 Scar/ WAVE, 38 formins, 39 various PAK-related kinases 40 and WASP. 41 It is remarkable, however, that the zones of GBD and DGAP1 localization are mutually exclusive, and that the dynamics of their local appearance and disappearance are exactly opposite to each other ( Fig. 2A).…”

Section: A Dual Role Model For Active Rac1 In Cell Migrationmentioning

confidence: 90%

A dual role model for active Rac1 in cell migration

Faix

Weber

2013

Small GTPases

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Section: A Dual Role Model For Active Rac1 In Cell Migrationmentioning

confidence: 90%

A dual role model for active Rac1 in cell migration

Faix

Weber

2013

Small GTPases

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“…Several signal transduction components are involved in regulating the actin-myosin cytoskeleton during chemotaxis, including phosphatidylinositol 3-kinase, PAK, WASP, and Ras (Tuxworth et al, 1997;Chung and Firtel, 1999;Lim et al, 2005;Myers et al, 2005). Mutants with deletions of the encoding genes suggest that none of these signaling pathways is essential but that each contributes to chemotaxis to a different extent.…”

Section: Discussionmentioning

confidence: 99%

Guanylyl Cyclase Protein and cGMP Product Independently Control Front and Back of ChemotaxingDictyosteliumCells

Veltman

Haastert

2006

MBoC

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Chemotaxis of amoeboid cells is driven by actin filaments in leading pseudopodia and actin-myosin filaments in the back and at the side of the cell to suppress pseudopodia. In Dictyostelium, cGMP plays an important role during chemotaxis and is produced predominantly by a soluble guanylyl cyclase (sGC). The sGC protein is enriched in extending pseudopodia at the leading edge of the cell during chemotaxis. We show here that the sGC protein and the cGMP product have different functions during chemotaxis, using two mutants that lose either catalytic activity (sGC⌬cat) or localization to the leading edge (sGC⌬N). Cells expressing sGC⌬N exhibit excellent cGMP formation and myosin localization in the back of the cell, but they exhibit poor orientation at the leading edge. Cells expressing the catalytically dead sGC⌬cat mutant show poor myosin localization at the back, but excellent localization of the sGC protein at the leading edge, where it enhances the probability that a new pseudopod is made in proximity to previous pseudopodia, resulting in a decrease of the degree of turning. Thus cGMP suppresses pseudopod formation in the back of the cell, whereas the sGC protein refines pseudopod formation at the leading edge. INTRODUCTIONChemotaxis is a vital process in a variety of organisms, ranging from bacteria to vertebrates. Prokaryotes use chemotaxis to move toward high nutrient concentrations or away from unfavorable conditions, whereas in eukaryotes chemotaxis is also involved in embryogenesis, wound healing, and the immune response. Chemotaxis is achieved by coupling gradient sensing to basic cell movement. Prokaryotes are too small to sense spatial gradients and therefore rely on temporal changes of the chemoattractant concentration to achieve chemotaxis. They do this by adjusting their tumbling frequency in response to temporal changes of the chemoattractant concentration (Szurmant and Ordal, 2004;Wadhams and Armitage, 2004). Eukaryotic cells are typically large enough to be able to measure a spatial gradient. The difference in receptor occupation between each side of the cell leads to an internal polarization. A pseudopod is extended at the side with the highest receptor occupation and at the same time, pseudopod formation at all other sides is repressed, resulting in directional cell migration (Devreotes and Janetopoulos, 2003;Postma et al., 2004).Dictyostelium is a eukaryotic organism that is widely used to study chemotaxis (Williams and Harwood, 2003;Parent, 2004;Affolter and Weijer, 2005). Starved Dictyostelium cells periodically secrete cAMP. Through relay of the cAMP signal by neighboring cells, concentric cAMP waves are generated. Starved Dictyostelium cells are chemotactically sensitive to cAMP and by movement in the direction of the origin of the cAMP waves, the cells are able to aggregate into groups of up to 100,000 cells. The chemotactic response of Dictyostelium is optimized for the dynamic cAMP waves that coordinate both aggregation and multicellular development. Cells show a much stronger chemotact...

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“…The Rac effector WAVE2, which is crucial for lamellipodium formation at the leading edge of chemotactic neutrophils [103][104][105][106], is also recruited to the plasma membrane in a PtdIns(3,4,5)P 3 -dependent manner [107]. N-WASP (neuronal WASP) as well as Dictyostelium WASP bind PtdIns(4,5)P 2 and PtdIns(3,4,5)P 3 , and PtdIns(3,4,5)P 3 binding promotes the localization of Dictyostelium WASP at the leading edge of chemotactic cells [107,108].…”

Section: Figure 3 Small Gtpases Similarly Regulate Actin and Myosin Dmentioning

confidence: 99%

Big roles for small GTPases in the control of directed cell movement

Charest

Firtel

2006

Biochemical Journal

179

156

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Small GTPases are involved in the control of diverse cellular behaviours, including cellular growth, differentiation and motility. In addition, recent studies have revealed new roles for small GTPases in the regulation of eukaryotic chemotaxis. Efficient chemotaxis results from co-ordinated chemoattractant gradient sensing, cell polarization and cellular motility, and accumulating data suggest that small GTPase signalling plays a central role in each of these processes as well as in signal relay. The present review summarizes these recent findings, which shed light on the molecular mechanisms by which small GTPases control directed cell migration.

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ADictyosteliumHomologue of WASP Is Required for Polarized F-Actin Assembly during Chemotaxis

Cited by 74 publications

References 73 publications

A dual role model for active Rac1 in cell migration

A dual role model for active Rac1 in cell migration

Guanylyl Cyclase Protein and cGMP Product Independently Control Front and Back of ChemotaxingDictyosteliumCells

Big roles for small GTPases in the control of directed cell movement

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