Expression of GFRα1 receptor splicing variants with different biochemical properties is modulated during kidney development

Nicolas Charlet-Berguerand, Hervé Le Hir, Mariarosaria Incoronato, Umberto Di Porzio, Yanbin Yu, Shuqian Jing, Vittorio De Franciscis, Claude Thermes

Research output: Contribution to journalArticle

Abstract

The glial cell line-derived neurotrophic factor (GDNF) family coreceptor α1 (GFRα1) is a critical component of the RET receptor kinase signal-transducing complex. The activity of this multicomponent receptor is stimulated by the glial cell line-derived neurotrophic factor (GDNF) and is involved in neuronal cells survival and kidney development. GFRα1 pre-mRNA is alternatively spliced and produces two isoforms: GFRα1a, which includes the exon 5; and GFRα1b, which excludes it. Here we show that the Gfrα1a isoform is predominantly expressed in neuronal tissues and in PC12 cells differentiated toward a neuronal phenotype. GFRα1 splicing is also regulated during kidney development, GFRα1a is the minor isoform before birth and then rapidly becomes the major form after birth. We established cell lines expressing either GFRα1 isoforms and demonstrated that the GFRα1b isoform binds GDNF more efficiently than GFRα1a. Consistently, GFRα1b promotes a stronger RET phosphorylation than GFRα1a. These results indicate that specific inclusion of the GFRα1 exon 5 in neuronal tissues or during kidney development may alter the binding properties of GDNF to GFRα1, and thus could constitute an additional regulatory mechanism of the RET signaling pathway.

Original languageEnglish
Pages (from-to)1425-1434
Number of pages10
JournalCellular Signalling
Volume16
Issue number12
DOIs
Publication statusPublished - Dec 2004

Keywords

  • Alternative splicing
  • GFRα1
  • Kidney development
  • RET

ASJC Scopus subject areas

  • Cell Biology

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