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Expression and alternative splicing of mouse Gfra4 suggest roles in endocrine cell development.

Molecular and cellular neurosciences (2000-06-22)
M Lindahl, T Timmusk, J Rossi, M Saarma, M S Airaksinen
ABSTRACT

Members of the GDNF protein family signal through receptors consisting of a GPI-linked GFRalpha subunit and the transmembrane tyrosine kinase Ret. Here we characterize the mouse Gfra4 and show that it undergoes developmentally regulated alternative splicing in several tissues. The mammalian GFRalpha4 receptor lacks the first Cys-rich domain characteristic of other GFRalpha receptors. Gfra4 is expressed in many tissues, including nervous system, in which intron retention leads to a putative intracellular or secreted GFRalpha4 protein. Efficient splicing occurs only in thyroid, parathyroid, and pituitary and less in adrenal glands. A splice form that leads to a GPI-linked GFRalpha4 receptor is expressed in juvenile thyroid and parathyroid glands. In newborn and mature thyroid as well as in parathyroid and pituitary glands major transcripts encode for a putative transmembrane isoform of GFRalpha4. Significant loss of thyroid C cells in Ret-deficient mice suggests that C cells and cells in adrenal medulla, which also express Ret, may require signaling via the GFRalpha4-Ret receptor. Finally, in human, GFRalpha4 expression may restrict the inherited cancer syndrome multiple endocrine neoplasia type 2, associated with mutations in RET, to these cells.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
GDNF from mouse, recombinant, expressed in E. coli, ≥98% (SDS-PAGE), ≥98% (HPLC), suitable for cell culture
Sigma-Aldrich
GDNF human, Animal-component free, recombinant, expressed in E. coli, ≥98% (SDS-PAGE), ≥98% (HPLC)
Sigma-Aldrich
GDNF from rat, recombinant, expressed in E. coli, ≥98% (SDS-PAGE), ≥98% (HPLC), suitable for cell culture
Sigma-Aldrich
Persephin human, recombinant, expressed in E. coli, ≥98% (SDS-PAGE), ≥98% (HPLC), suitable for cell culture
Sigma-Aldrich
Persephin from mouse, recombinant, expressed in E. coli, ≥98% (SDS-PAGE), ≥98% (HPLC), suitable for cell culture

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