Temporal and Spatial Regulation of Chemotaxis

Iijima, Miho; Huang, Yi Elaine; Devreotes, Peter N.

doi:10.1016/s1534-5807(02)00292-7

Cited by 308 publications

(235 citation statements)

References 83 publications

Supporting

Mentioning

226

Contrasting

Unclassified

Order By: Relevance

“…PI3-Kinase is emerging as a key regulator of cell polarity and chemotactic migration (reviewed by Iijima et al, 2002). PI3-Kinase is the major effector of R-Ras (Marte et al, 1996) and uncoupling of this effector from R-Ras rescued membrane protrusion and migration across collagen (Figure 10).…”

Section: Discussionmentioning

confidence: 99%

R-Ras Controls Membrane Protrusion and Cell Migration through the Spatial Regulation of Rac and Rho

Wozniak

Kwong

Chodniewicz

et al. 2005

MBoC

View full text Add to dashboard Cite

Although it is known that the spatial coordination of Rac and Rho activity is essential for cell migration, the molecular mechanisms regulating these GTPases during migration are unknown. We found that the expression of constitutively activated R-Ras (38V) blocked membrane protrusion and random migration. In contrast, expression of dominant negative R-Ras (41A) enhanced migrational persistence and membrane protrusion. Endogenous R-Ras is necessary for cell migration, as cells that were transfected with siRNA for R-Ras did not migrate. Expression of R-Ras (38V) decreased Rac activity and increased Rho activity around the entire cell periphery, whereas expression of dominant negative R-Ras (41A) showed the converse, suggesting that R-Ras can spatially activate Rho and inactivate Rac. Consistent with this role, endogenous R-Ras localized and was preferentially activated at the leading edge of migratory cells in response to adhesion. The effects of R-Ras on cell migration are mediated by PI3-Kinase, as an effector mutant that uncouples PI3-Kinase binding from R-Ras (38V) rescued migration. From these data, we hypothesize that R-Ras plays a key role in cell migration by locally regulating the switch from Rac to Rho activity after membrane protrusion and adhesion.

show abstract

Section: Discussionmentioning

confidence: 99%

R-Ras Controls Membrane Protrusion and Cell Migration through the Spatial Regulation of Rac and Rho

Wozniak

Kwong

Chodniewicz

et al. 2005

MBoC

View full text Add to dashboard Cite

show abstract

“…Candidates for such regulatory roles include members of the Rho-GTPase family of molecules, such as Rho and Rac1, which translate external signals into alterations in cytoskeletal reorganization and hence have the ability to influence migration. A large body of literature has characterized the cellular mechanisms and signal transduction pathways of Rho, Rho-dependent kinase (ROCK) and related regulatory members, such as Rac and PI3K, on cellular motility and chemotaxis in various cell types [29][30][31][32][33][34][35][36].…”

Section: Introductionmentioning

confidence: 99%

The Rho Kinase Pathway Regulates Mouse Adult Neural Precursor Cell Migration

et al. 2011

View full text Add to dashboard Cite

Adult neural precursor cells (NPCs) in the subventricular zone (SVZ) normally migrate via the rostral migratory stream (RMS) to the olfactory bulb (OB). Following neural injury, they also migrate to the site of damage. This study investigated the role of Rho-dependent kinase (ROCK) on the migration of NPCs in vitro and in vivo. In vitro, using neurospheres or SVZ explants, inhibition of ROCK using Y27632 promoted cell body elongation, process protrusion, and migration, while inhibiting NPC chain formation. It had no effect on proliferation, apoptosis, or differentiation. Both isoforms of ROCK were involved. Using siRNA, knockdown of both ROCK1 and ROCK2 was required to promote NPC migration and morphological changes; knockdown of ROCK2 alone was partially effective, with little/no effect of knockdown of ROCK1 alone. In vivo, infusion of Y27632 plus Bromodeoxyuridine (BrdU) into the lateral ventricle for 1 week reduced the number of BrdU-labeled NPCs in the OB compared with BrdU infusion alone. However, ROCK inhibition did not affect the tangential-to-radial switch of NPC migration, as labeled cells were present in all OB layers. The decrease in NPC number at the OB was not attributed to a decrease in NPCs at the SVZ. However, ROCK inhibition decreased the density of BrdU-labeled cells in the RMS and increased the distribution of these cells to ectopic brain regions, such as the accessory olfactory nucleus, where the majority differentiated into neurons. These findings suggest that ROCK signaling regulates NPC migration via regulation of cell-cell contact and chain migration.

show abstract

“…Cells show a much stronger chemotactic response to a cAMP wave, where the mean concentration increases over time, than to a static spatial gradient. Dictyostelium uses both spatial gradient sensing and the "bacterial-like" temporal gradient sensing to respond to these dynamic chemoattractant gradients (Futrelle, 1982;Varnum-Finney et al, 1987;Iijima et al, 2002;Xu et al, 2005).The signal transduction pathways that are coupled to spatial gradient sensing and temporal gradient sensing rely on signal molecules with differential physical properties. Molecules that store spatial information have low diffusion rates to prevent the information from simply diffusing away.…”

mentioning

confidence: 99%

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

Veltman

Haastert

2006

MBoC

View full text Add to dashboard Cite

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...

show abstract

Temporal and Spatial Regulation of Chemotaxis

Cited by 308 publications

References 83 publications

R-Ras Controls Membrane Protrusion and Cell Migration through the Spatial Regulation of Rac and Rho

R-Ras Controls Membrane Protrusion and Cell Migration through the Spatial Regulation of Rac and Rho

The Rho Kinase Pathway Regulates Mouse Adult Neural Precursor Cell Migration

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

Contact Info

Product

Resources

About