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

doi:10.1016/j.febslet.2004.06.007

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

FEBS Lett. 2004 Jul 2;569(1-3):267-71. doi: 10.1016/j.febslet.2004.06.007.

Authors

Jianmin Yang¹, Maria Lindahl, Päivi Lindholm, Heidi Virtanen, Eleanor Coffey, Pia Runeberg-Roos, Mart Saarma

Affiliation

¹ Institute of Biotechnology, Viikki Biocenter, University of Helsinki, Viikinkaari 9, P.O. Box 56, FIN-00014 Helsinki, Finland.

PMID: 15225646
DOI: 10.1016/j.febslet.2004.06.007

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.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

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 Glycoproteins / metabolism*
Membrane Microdomains / metabolism*
Mice
Nerve Growth Factors / metabolism*
Nerve Tissue Proteins / metabolism*
Neurites / physiology*
Neurons / cytology
Neurons / physiology*
Proto-Oncogene Proteins / genetics
Proto-Oncogene Proteins / metabolism*
Proto-Oncogene Proteins c-ret
Rats
Receptor Protein-Tyrosine Kinases / genetics
Receptor Protein-Tyrosine Kinases / metabolism*
Receptors, Nerve Growth Factor / genetics
Receptors, Nerve Growth Factor / metabolism*
Recombinant Proteins / metabolism
Transfection

Substances

GDNF protein, human
GFRA1 protein, human
GFRA4 protein, human
Gdnf protein, mouse
Gdnf protein, rat
Gfra1 protein, mouse
Glial Cell Line-Derived Neurotrophic Factor
Glial Cell Line-Derived Neurotrophic Factor Receptors
Membrane Glycoproteins
Nerve Growth Factors
Nerve Tissue Proteins
Proto-Oncogene Proteins
Receptors, Nerve Growth Factor
Recombinant Proteins
persephin
Proto-Oncogene Proteins c-ret
Receptor Protein-Tyrosine Kinases
Ret protein, mouse
Ret protein, rat