PSPN/GFRalpha4 has a significantly weaker capacity than GDNF/GFRalpha1 to recruit RET to rafts, but promotes neuronal survival and neurite outgrowth

Jianmin Yang, Maria Lindahl, Päivi Lindholm, Heidi Virtanen, Eleanor Coffey, Pia Runeberg-Roos, Mart Saarma

Research output: Contribution to journalArticleScientificpeer-review

16 Citations (Scopus)

Abstract

Previously, it was shown that the recruitment of RET into lipid rafts by glial cell line-derived neurotrophic factor (GDNF)/GFRalpha1 is crucial for efficient signal transduction. Here, we show that the mouse GFRalpha4 is a functional, N-glycosylated, glycosylphosphatidylinositol (GPI)-anchored protein, which mediates persephin (PSPN)-induced phosphorylation of RET, but has an almost undetectable capacity to recruit RET into the 0.1% Triton X-100 insoluble membrane fraction. In spite of this, PSPN/mGFRalpha4 promotes neurite outgrowth in PC6-3 cells and survival of cerebellar granule neurons. As we show that also human PSPN/GFRalpha4 is unable to recruit RET into lipid rafts, we propose that the mammalian GFRalpha4 in this respect differs from GFRalpha1.

Original languageEnglish
Pages (from-to)267-71
Number of pages5
JournalFEBS Letters
Volume569
Issue number1-3
DOIs
Publication statusPublished - 2 Jul 2004
MoE publication typeA1 Journal article-refereed

Keywords

  • Animals
  • Cell Line
  • Cell Membrane/physiology
  • Cloning, Molecular
  • Glial Cell Line-Derived Neurotrophic Factor
  • Glial Cell Line-Derived Neurotrophic Factor Receptors
  • Humans
  • Membrane Glycoproteins/genetics
  • Membrane Microdomains/metabolism
  • Mice
  • Nerve Growth Factors/metabolism
  • Nerve Tissue Proteins/metabolism
  • Neurites/physiology
  • Neurons/cytology
  • Proto-Oncogene Proteins/genetics
  • Proto-Oncogene Proteins c-ret
  • Rats
  • Receptor Protein-Tyrosine Kinases/genetics
  • Receptors, Nerve Growth Factor/genetics
  • Recombinant Proteins/metabolism
  • Transfection

Fingerprint

Dive into the research topics of 'PSPN/GFRalpha4 has a significantly weaker capacity than GDNF/GFRalpha1 to recruit RET to rafts, but promotes neuronal survival and neurite outgrowth'. Together they form a unique fingerprint.

Cite this