A pair as a minimum: The two fibroblast growth factors of the nematode <i>Caenorhabditis elegans</i>

Birnbaum, Daniel; Popovici, Cornel; Roubin, Régine

doi:10.1002/dvdy.20219

Cited by 35 publications

(33 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Some of the key signaling molecules that have been implicated in longitudinal guidance include the fibroblast growth factor EGL-17/FGF (Burdine et al 1997) and its receptor EGL-15/FGFR (Devore et al 1995;Bulow et al 2004;Birnbaum et al 2005), LIN-17/Frizzled (Hilliard and Bargmann 2006), the Wnts LIN-44, CWN-1, CWN-2, and EGL-20 (Maloof et al 1999;Zinovyeva et al 2008), and UNC-53/NAV2, a cytoskeletal binding protein related to the mammalian neuronal navigators (NAVs) (Stringham and Schmidt 2009). Loss-offunction mutations in unc-53 cause both anterior and posterior extension and guidance defects in several cell types including the axons of the mechanosensory neurons (Hekimi and Kershaw 1993), the excretory canals (Hedgecock et al 1990;Stringham et al 2002), and the sex myoblasts (Stringham et al 2002).…”

mentioning

confidence: 99%

Distinct Cell Guidance Pathways Controlled by the Rac and Rho GEF Domains of UNC-73/TRIO in Caenorhabditis elegans

2012

View full text Add to dashboard Cite

The cytoskeleton regulator UNC-53/NAV2 is required for both the anterior and posterior outgrowth of several neurons as well as that of the excretory cell while the kinesin-like motor VAB-8 is essential for most posteriorly directed migrations in Caenorhabditis elegans. Null mutations in either unc-53 or vab-8 result in reduced posterior excretory canal outgrowth, while double null mutants display an enhanced canal extension defect, suggesting the genes act in separate pathways to control this posteriorly directed outgrowth. Genetic analysis of putative interactors of UNC-53 or VAB-8, and cell-specific rescue experiments suggest that VAB-8, SAX-3/ROBO, SLT-1/Slit, and EVA-1 are functioning together in the outgrowth of the excretory canals, while UNC-53 appears to function in a parallel pathway with UNC-71/ADAM. The known VAB-8 interactor, the Rac/Rho GEF UNC-73/TRIO operates in both pathways, as isoform specific alleles exhibit enhancement of the phenotype in double-mutant combination with either unc-53 or vab-8. On the basis of these results, we propose a bipartite model for UNC-73/TRIO activity in excretory canal extension: a cell autonomous function that is mediated by the Rho-specific GEF domain of the UNC-73E isoform in conjunction with UNC-53 and UNC-71 and a cell nonautonomous function that is mediated by the Rac-specific GEF domain of the UNC-73B isoform, through partnering with VAB-8 and the receptors SAX-3 and EVA-1.

show abstract

mentioning

confidence: 99%

Distinct Cell Guidance Pathways Controlled by the Rac and Rho GEF Domains of UNC-73/TRIO in Caenorhabditis elegans

2012

View full text Add to dashboard Cite

show abstract

“…3 The constitutive expression of egl-15 includes exon 5B and the resulting protein binds to the fibroblast growth factor LET-756 (Fig. 1).…”

mentioning

confidence: 99%

Splicing factor SUP-12 and the molecular complexity of apparent cooperativity

Mackereth

2014

Worm

View full text Add to dashboard Cite

T he splicing factor SUP-12 from C. elegans, in combination with either ASD-1 or FOX-1 from the Fox-1 (RBFOX) family, is required for generating a muscle-specific isoform of the fibroblast growth factor receptor EGL-15. Biophysical techniques have revealed the sequence preference for the RNA Recognition Motif (RRM) domain from SUP-12 as well as the structural details of the RNA-bound complex. Detailed genetics have identified a requisite need for the presence of both SUP-12 and ASD-1/FOX-1 to regulate the alternative splicing event, prompting speculation of a cooperative mechanism between these proteins on binding RNA. In contrast, the interplay between SUP-12 and ASD-1 suggests that although the RRM domains from each protein are in direct contact on the egl-15 pre-mRNA, there is no simple contribution of binding cooperativity. Evidence for an independent binding mechanism by SUP-12 and ASD-1 will be discussed, including a model in which both positive and negative contributions are balanced during complex assembly. The ability to monitor tissue-specific alternative splicing in live nematodes will continue to provide a powerful method to test in vivo mechanistic models derived from atomic-level investigation.Interactions between cellular biomolecules such as proteins and nucleic acids are critical for life, and the precise regulation of these interactions in a time-and location-dependent manner allows for normal organism development.Alternative splicing can contribute to this process through the production of development-and tissuespecific protein isoforms. The spliceosome generally interacts with target premRNA with the help of constitutive protein trans factors that recognize RNA cis elements in order to define the intron boundaries and dictate the series of exons in the mature mRNA. To regulate this process, additional splicing factors also bind to the pre-mRNA in order to enhance or inhibit specific 5 0 and 3 0 intron splice sites. The mechanisms by which the final splice patterns are established are in general poorly understood, but predominantly involve cooperative or competitive interactions with the constitutive splicing machinery to alter spliceosome recruitment, premRNA motif availability or the catalytic efficiency.Several splicing factors have already been identified in C. elegans that display limited expression patterns and lead to cell type-specific changes in splicing regulation.1 In many cases, multiple factors are linked to a specific splicing event, including both positive and negative regulators that together dictate the final pattern of exon retention in the mature mRNA. 2Structures of RNA-binding domains from splicing proteins shed light on the basis for RNA motif preference and this information can explain the phenotypic effects of known genetic variations in the protein factors or RNA elements. The molecular details also help in the strategic design of mutants to selectively perturb the contribution of a splicing factor in a given splicing event. Less known are the atomic details that under...

show abstract

“…EGL-15/FGFR has two differentially expressed isoforms EGL-15 (5A) and EGL- 15 (5B), due to alternative splicing of the fifth exon. The intracellular signaling cascades activated by EGL-15 are relatively well characterized and share a high degree of conservation with mammalian FGFRs (15,16). Loss of function in egl- 15 (5B)/fgfr or in let-756/fgf lead to larval lethality, but the exact cause of this lethality is not known.…”

mentioning

confidence: 99%

“…The intracellular signaling cascades activated by EGL-15 are relatively well characterized and share a high degree of conservation with mammalian FGFRs (15,16). Loss of function in egl- 15 (5B)/fgfr or in let-756/fgf lead to larval lethality, but the exact cause of this lethality is not known. EGL-15/FGFR signaling is negatively regulated by a receptor phosphatase, CLR-1 (17) and by N-glycosylation of the extracellular domain of EGL-15 (18).…”

mentioning

confidence: 99%

“…Whereas in mammals the morphogen and endocrine functions of FGFs have diverged, the role of EGL-15/FGFR signaling in fluid homeostasis and the suggested action of LET-756 as a paracrine factor (15), raise the intriguing possibility of parallel morphogen and endocrine functions for the C. elegans FGFs EGL-17 and LET-756. The C. elegans excretory cell is a large H-shaped cell with structural and functional parallels with the mammalian kidney (22,23).…”

mentioning

confidence: 99%

See 1 more Smart Citation

The Cooperation of FGF Receptor and Klotho Is Involved in Excretory Canal Development and Regulation of Metabolic Homeostasis in Caenorhabditis elegans

Polanska

Edwards

Fernig

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

A pair as a minimum: The two fibroblast growth factors of the nematode Caenorhabditis elegans

Cited by 35 publications

References 67 publications

Distinct Cell Guidance Pathways Controlled by the Rac and Rho GEF Domains of UNC-73/TRIO in Caenorhabditis elegans

Distinct Cell Guidance Pathways Controlled by the Rac and Rho GEF Domains of UNC-73/TRIO in Caenorhabditis elegans

Splicing factor SUP-12 and the molecular complexity of apparent cooperativity

The Cooperation of FGF Receptor and Klotho Is Involved in Excretory Canal Development and Regulation of Metabolic Homeostasis in Caenorhabditis elegans

Contact Info

Product

Resources

About