Son of Sevenless Directly Links the Robo Receptor to Rac Activation to Control Axon Repulsion at the Midline

Yang, Long; Bashaw, Greg J.

doi:10.1016/j.neuron.2006.09.039

Cited by 89 publications

(95 citation statements)

References 48 publications

(73 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, the axon defects found in vav;trio double mutants are reminiscent of those observed in triple loss-of-function Rac mutants (Hakeda-Suzuki et al, 2002). Sos is another GEF that have been implicated in axon guidance during embryonic CNS formation through the activation of Rac (Yang and Bashaw, 2006). Removal of sos results in midline crossing defects similar to those described here for vav (Fritz and VanBerkum, 2000) and (Fig.…”

Section: Genetic Interactions Between Vav and Other Gefssupporting

confidence: 71%

“…For instance, beside its function in longitudinal axon growth, Trio has been involved in promoting commissure formation through its interaction with the attractive Netrin receptor Frazzled (Forsthoefel et al, 2005). Furthermore, another GEF, Sos, has been proposed to mediate Rac activation downstream of the Robo receptor to control axon repulsion at the midline (Yang and Bashaw, 2006). In this scenario, Vav, Sos, and Trio could coexist and be activated in response to different guidance molecules to control distinct aspects of axon guidance during the formation of the CNS.…”

Section: Vav and Other Gefsmentioning

confidence: 99%

See 1 more Smart Citation

The Guanine Exchange FactorvavControls Axon Growth and Guidance duringDrosophilaDevelopment

Malartre

Ayaz²,

Amador³

et al. 2010

J. Neurosci.

View full text Add to dashboard Cite

The Vav proteins are guanine exchange factors (GEFs) that trigger the activation of the Rho GTPases in general and the Rac family in particular. While the role of the mammalian vav genes has been extensively studied in the hematopoietic system and the immune response, there is little information regarding the role of vav outside of these systems. Here, we report that the single Drosophila vav homolog is ubiquitously expressed during development, although it is enriched along the embryonic ventral midline and in the larval eye discs and brain. We have analyzed the role that vav plays during development by generating Drosophila null mutant alleles. Our results indicate that vav is required during embryogenesis to prevent longitudinal axons from crossing the midline. Later on, during larval development, vav is required within the axons to regulate photoreceptor axon targeting to the optic lobe. Finally, we demonstrate that adult vav mutant escapers, which exhibit coordination problems, display axon growth defects in the ellipsoid body, a brain area associated with locomotion control. In addition, we show that vav interacts with other GEFs known to act downstream of guidance receptors. Thus, we propose that vav acts in coordination with other GEFs to regulate axon growth and guidance during development by linking guidance signals to the cytoskeleton via the modulation of Rac activity.

show abstract

Section: Genetic Interactions Between Vav and Other Gefssupporting

confidence: 71%

Section: Vav and Other Gefsmentioning

confidence: 99%

The Guanine Exchange FactorvavControls Axon Growth and Guidance duringDrosophilaDevelopment

Malartre

Ayaz²,

Amador³

et al. 2010

J. Neurosci.

View full text Add to dashboard Cite

show abstract

“…10, C and D). Accordingly, it has been shown that in both mammalian cells and Drosophila embryos Slit activates Rac-1 by recruiting the guanine-nucleotide exchange factor (GEF) Sos to Robo (Fan et al, 2003;Yang and Bashaw, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…During axon guidance the repulsive action of Slit-2 is mediated, among other factors, by changes in the activity of Cdc-42 and Rac-1, two members of the Rho-like family of small GTPases (Wong et al, 2001;Fan et al, 2003;Yang and Bashaw, 2006). Because Rac-1 is required for production and stabilization of cell-cell contacts (Sahai and Marshall, 2002) and Cdc-42 is a well-known inducer of filopodia formation (Nobes and Hall, 1995), we speculated that the reduced strength of intercellular junctions and the increased production of filopodia observed in Slit-2-deficient cells could be due to a Figure 7.…”

Section: Effects Of the Modulation Of The Slit/robo Pathway On Hgf-dementioning

confidence: 99%

The Slit/Robo System Suppresses Hepatocyte Growth Factor-dependent Invasion and Morphogenesis

Stella

Trusolino

Comoglio

2009

MBoC

View full text Add to dashboard Cite

The Slit protein acts through the Roundabout receptor as a paracrine chemorepellent in axon guidance and as an inhibitor in leukocyte chemotaxis, but its role in epithelial cell motility and morphogenesis remains largely unexplored. We report that nontransformed epithelial cells and cancerous cells empower the Slit-2/Robo1 signaling system to limit outward migration in response to motogenic attractants and to remain positionally confined within their primitive location. Short hairpin RNA-mediated depletion of SLIT-2 or ectopic expression of a soluble decoy Robo enhance hepatocyte growth factor (HGF)-induced migration, matrix invasion, and tubulogenesis, concomitantly with the up-regulation of Cdc-42 and the down-modulation of Rac-1 activities. Accordingly, autocrine overexpression or exogenous administration of Slit-2 prevent HGF-triggered motile responses, reduce Cdc-42 activation, and stimulate Rac-1. This antimigratory activity of Slit-2 derives from the inhibition of actin-based protrusive forces and from an increased adhesive strength of cadherinmediated intercellular contacts. These results disclose a novel function for Slit and Robo in the inhibition of growth factor-mediated epithelial cell motility and morphogenesis, invoking a critical role for both molecules as natural antagonists of neoplastic invasive growth.

show abstract

“…For each group of cells, at least 10 cells were randomly selected for quantification. Average fluorescence intensity was calculated using NIH Image J software, as previously described (Yang and Bashaw, 2006).…”

Section: Cell Immunofluorescencementioning

confidence: 99%

The Adam family metalloprotease Kuzbanian regulates the cleavage of the roundabout receptor to control axon repulsion at the midline

et al. 2010

Self Cite

View full text Add to dashboard Cite

SUMMARYSlits and their Roundabout (Robo) receptors mediate repulsive axon guidance at the Drosophila ventral midline and in the vertebrate spinal cord. Slit is cleaved to produce fragments with distinct signaling properties. In a screen for genes involved in Slit-Robo repulsion, we have identified the Adam family metalloprotease Kuzbanian (Kuz). Kuz does not regulate midline repulsion through cleavage of Slit, nor is Slit cleavage essential for repulsion. Instead, Kuz acts in neurons to regulate repulsion and Kuz can cleave the Robo extracellular domain in Drosophila cells. Genetic rescue experiments using an uncleavable form of Robo show that this receptor does not maintain normal repellent activity. Finally, Kuz activity is required for Robo to recruit its downstream signaling partner, Son of sevenless (Sos). These observations support the model that Kuz-directed cleavage is important for Robo receptor activation.

show abstract

Son of Sevenless Directly Links the Robo Receptor to Rac Activation to Control Axon Repulsion at the Midline

Cited by 89 publications

References 48 publications

The Guanine Exchange FactorvavControls Axon Growth and Guidance duringDrosophilaDevelopment

The Guanine Exchange FactorvavControls Axon Growth and Guidance duringDrosophilaDevelopment

The Slit/Robo System Suppresses Hepatocyte Growth Factor-dependent Invasion and Morphogenesis

The Adam family metalloprotease Kuzbanian regulates the cleavage of the roundabout receptor to control axon repulsion at the midline

Contact Info

Product

Resources

About