GDNF promotes tubulogenesis of GFRα1-expressing MDCK cells by Src-mediated phosphorylation of Met receptor tyrosine kinase

Popsueva, Anna; Poteryaev, Dmitry; Arighi, Elena; Meng, Xiaojuan; Angers-Loustau, Alexandre; Kaplan, David R.; Saarma, Märt; Sariola, Hannu

doi:10.1083/jcb.200212174

Cited by 85 publications

(64 citation statements)

References 57 publications

(76 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Gfra1 is coexpressed with Ret, consistent with its role as a co-receptor, and it can also mediate GDNF signaling independently of Ret in some circumstances. (23)(24)(25) Although Gfra1 is expressed in a slightly broader domain of the UB, and also to some extent in the mesenchyme and forming nephrons, (21,22,26) its expression in cells outside the Ret domain is entirely dispensable for normal kidney development; this was shown by targeting Gfra1 coding sequences into the Ret locus, so it was expressed in the pattern of Ret, and crossing these mice to animals lacking endogenous Gfra1. (27) The key role of GDNF and its receptors in kidney development was initially revealed by the targeted disruption of the Ret, GDNF and Gfra1 genes.…”

Section: Introductionmentioning

confidence: 99%

GDNF/Ret signaling and the development of the kidney

2006

View full text Add to dashboard Cite

SummarySignaling by GDNF through the Ret receptor is required for normal growth of the ureteric bud during kidney development. However, the precise role of GDNF/Ret signaling in renal branching morphogenesis and the specific responses of ureteric bud cells to GDNF remain unclear. Recent studies have provided new insight into these issues. The localized expression of GDNF by the metanephric mesenchyme, together with several types of negative regulation, is important to elicit and correctly position the initial budding event from the Wolffian duct. GDNF also promotes the continued branching of the ureteric bud. However, it does not provide the positional information required to specify the pattern of ureteric bud growth and branching, as its site of synthesis can be drastically altered with minimal effects on kidney development. Cells that lack Ret are unable to contribute to the tip of the ureteric bud, apparently because GDNF-driven proliferation is required for the formation and growth of this specialized epithelial domain.

show abstract

Section: Introductionmentioning

confidence: 99%

GDNF/Ret signaling and the development of the kidney

2006

View full text Add to dashboard Cite

show abstract

“…22 It is likewise possible that FGF7 expression is upregulated in Ret Ϫ/Ϫ kidneys with UB formation. We found that the expression level of FGF7 was higher in a Ret Ϫ/Ϫ kidney with discernible UB compared with Ret ϩ/Ϫ or wild-type kidneys ( Figure 5N), raising the possibility that upregulation of FGF7 in Ret null kidneys contributes to the formation of the UB in these mice.…”

Section: Bead Experiments To Determine the Role Of Fgf7/ Follistatin mentioning

confidence: 99%

Glial Cell–Derived Neurotrophic Factor–Independent Ureteric Bud Outgrowth from the Wolffian Duct

Maeshima

Sakurai

Choi

et al. 2007

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

The kidney collecting duct system and the ureter derive from the ureteric bud, an outgrowth of the Wolffian duct. It is generally believed that glial cell-derived neurotrophic factor (GDNF) plays a critical role in this earliest stage of kidney development, but 30 to 50% of knockout mice that lack either Gdnf or one of its receptors, such as Ret, have normal ureters. This suggests that an alternative pathway can induce ureteric bud outgrowth from the Wolffian duct. Isolated Wolffian ducts were cultured, and it was found that a combination of fibroblast growth factor 7 (FGF7) and blockade of the TGF-␤ superfamily member activin A induced formation of buds from the Wolffian duct. This occurred even in the presence of a neutralizing anti-GDNF antibody or in Ret-knockout-derived Wolffian ducts, suggesting GDNFindependent induction of bud formation. Similar to wild-type ureteric buds or those induced by GDNF, FGF7/follistatin-induced buds were shown to be functionally competent, as they underwent branching morphogenesis and induced nephron formation upon recombination with metanephric mesenchyme. These in vitro findings suggest that modulation by FGF7 and the activin A signaling pathway, or equivalent pathways, can lead to GDNF-independent induction of ureteric bud outgrowth, possibly explaining the seemingly normal ureteric bud outgrowth in Gdnf or Ret null mice.

show abstract

“…NGFmediated Ret upregulation contributes considerably to the growth and metabolism-enhancing function of NGF on adult neurons (Tsui-Pierchala et al, 2002a). In addition to cross-talk signaling between NGF and Ret, other mechanisms of cross talk have been uncovered among other neurotrophic factor receptor pathways and between G-protein-coupled receptors (Lee and Chao, 2001;Lee et al, 2002;Popsueva et al, 2003). This implies that the elucidation of molecules responsible for communication between receptor signaling pathways will have widespread significance.…”

Section: Introductionmentioning

confidence: 99%

CD2AP and Cbl-3/Cbl-c Constitute a Critical Checkpoint in the Regulation of Ret Signal Transduction

Tsui¹,

Pierchala

2008

J. Neurosci.

View full text Add to dashboard Cite

The glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs) are critical for nervous system development and maintenance. GFLs promote survival and growth via activation of the receptor tyrosine kinase (RTK) Ret. In sympathetic neurons, the duration of Ret signaling is governed by how rapidly Ret is degraded after its activation. In an effort to elucidate mechanisms that control the half-life of Ret, we have identified two novel Ret interactors, CD2-associated protein (CD2AP) and Cbl-3. CD2AP, an adaptor molecule involved in the internalization of ubiquitinated RTKs, is associated with Ret under basal, unstimulated conditions in neurons. After Ret activation by GDNF, CD2AP dissociates. Similarly, the E3-ligase Cbl-3 interacts with unphosphorylated Ret and dissociates from Ret after Ret activation. In contrast to their dissociation from autophosphorylated Ret, an interaction between CD2AP and Cbl-3 is induced by GDNF stimulation of sympathetic neurons, suggesting that CD2AP and Cbl-3 dissociate from Ret as a complex. In neurons, the overexpression of CD2AP enhances the degradation of Ret and inhibits GDNF-dependent survival, and gene silencing of CD2AP blocks Ret degradation and promotes GDNF-mediated survival. Surprisingly, Cbl-3 overexpression dramatically stabilizes activated Ret and enhances neuronal survival, even though Cbl-family E3 ligases normally function to trigger RTK downregulation. In combination with CD2AP, however, Cbl-3 promotes Ret degradation rapidly and almost completely blocks survival promotion by GDNF, suggesting that Cbl-3 acts as a switch that is triggered by CD2AP and oscillates between inhibition and promotion of Ret degradation. Consistent with the hypothesis, Cbl-3 silencing in neurons only inhibited Ret degradation and enhanced neuronal survival in combination with CD2AP silencing. CD2AP and Cbl-3, therefore, constitute a checkpoint that controls the extent of Ret downregulation and, thereby, the sensitivity of neurons to GFLs.

show abstract

GDNF promotes tubulogenesis of GFRα1-expressing MDCK cells by Src-mediated phosphorylation of Met receptor tyrosine kinase

Cited by 85 publications

References 57 publications

GDNF/Ret signaling and the development of the kidney

GDNF/Ret signaling and the development of the kidney

Glial Cell–Derived Neurotrophic Factor–Independent Ureteric Bud Outgrowth from the Wolffian Duct

CD2AP and Cbl-3/Cbl-c Constitute a Critical Checkpoint in the Regulation of Ret Signal Transduction

Contact Info

Product

Resources

About