Retention in the Golgi apparatus and expression on the cell surface of Cfr/Esl-1/Glg-1/MG-160 are regulated by two distinct mechanisms

Abstract

Cfr (cysteine-rich fibroblast growth factor receptor) is an Fgf (fibroblast growth factor)-binding protein without a tyrosine kinase. We have shown previously that Cfr is involved in Fgf18 signalling via Fgf receptor 3c. However, as Cfr is also known as Glg (Golgi apparatus protein)-1 or MG-160 and occurs in the Golgi apparatus, it remains unknown how the distribution of Cfr is regulated. In the present study, we performed a mutagenic analysis of Cfr to show that two distinct regions contribute to its distribution and stability. First, the C-terminal region retains Cfr in the Golgi apparatus. Secondly, the Cfr repeats in the extracellular juxtamembrane region destabilizes Cfr passed through the Golgi apparatus. This destabilization does not depend on the cleavage and secretion of the extracellular domain of Cfr. Furthermore, we found that Cfr with a GPI (glycosylphosphatidylinositol) anchor was predominantly expressed on the cell surface in Ba/F3 cells and affected Fgf18 signalling in a similar manner to the full-length Cfr, indicating that the interaction of Cfr with Fgfs on the cell surface is important for its function in Fgf signalling. These results suggest that the expression of Cfr in the Golgi apparatus and on the plasma membrane is finely tuned through two distinct mechanisms for exhibiting different functions.

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“…The golgi apparatus protein 1 (GLG1), also known as CFR, ESL-1 and MG-160, is a 135 kDa glycosylated single pass type I transmembrane protein that contains 16 cysteine-rich GLG1 repeats [41]. It is found in the golgi apparatus and on the cell surface membrane.…”

“…GLG1 is able to bind with many different proteins making it an important regulatory protein and signal transducer. The localisation of GLG1 is a crucial determinant of GLG1 function and is influenced by two mechanisms: the transmembrane domain and cytoplasmic tail retain GLG1 in the golgi apparatus, whereas the cys-rich repeats destabilise the protein and GLG1 is recruited to the cell surface via processes of stability control [41]. It has also been reported that GLG1 can be released from the cell by proteolytic cleavage at the juxtamembrane region [42].…”