Alternative splicing affecting a novel domain in the C. elegans EGL-15 FGF receptor confers functional specificity.
Fibroblast growth factor (FGF) receptors trigger a wide variety of cellular responses as diverse as cell migration, cell proliferation and cell differentiation. However, the molecular basis of the specificity of these responses is not well understood. The C. elegans FGF receptor EGL-15 similarly mediates a number of different responses, including transducing a chemoattractive signal and mediating an essential function. Analysis of the migration-specific alleles of egl-15 has identified a novel EGL-15 isoform that provides a molecular explanation for the different phenotypic effects of lesions at this locus. Alternative splicing yields two EGL-15 proteins containing different forms of a domain located within the extracellular region of the receptors immediately after the first IG domain. Neither of these two domain forms is found in any other FGF receptor. We have tested the roles of these EGL-15 receptor isoforms and their two FGF ligands for their signaling specificity. Our analyses demonstrate different physiological functions for the two receptor variants. EGL-15(5A) is required for the response to the FGF chemoattractant that guides the migrating sex myoblasts to their final positions. By contrast, EGL-15(5B) is both necessary and sufficient to elicit the essential function mediated by this receptor.
Goodman
S Jay
SJ
Department of Cell Biology, Yale University School of Medicine, I-354 SHM PO Box 208005, New Haven, CT 06520-8005, USA.
Branda
Catherine S
CS
Robinson
Matthew K
MK
Burdine
Rebecca D
RD
Stern
Michael J
MJ
D017398:Alternative Splicing; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002633:Chemotaxis / Q000502:physiology; D008024:Ligands; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D019076:Transgenes
D029742:Caenorhabditis elegans Proteins; C112493:EGL-15 protein, C elegans; D008024:Ligands; D020033:Protein Isoforms; D017468:Receptors, Fibroblast Growth Factor