TY - JOUR
T1 - Biglycan is a novel binding partner of fibroblast growth factor receptor 3c (FGFR3c) in the human testis
AU - Winge, S B
AU - Nielsen, J
AU - Jørgensen, Anders
AU - Jacobsen, Sylwia Owczarek
AU - Ewen, K A
AU - Nielsen, J E
AU - Juul, Anders
AU - Berezin, V
AU - Meyts, Ewa Rajpert-De
N1 - Corrigendum to “Biglycan is a novel binding partner of fibroblast growth factor receptor 3c (FGFR3c) in the human testis”
It was discovered after final publication that legends to supplementary figures have been inadvertently embedded into the Results section. All initial text of the Results and legends to regular figures remain otherwise unchanged.
PY - 2015/1/5
Y1 - 2015/1/5
N2 - Regulation of spermatogonial maintenance in the human testis is currently not well understood. One pathway suggested to be involved is activated by fibroblast growth factor receptor 3 (FGFR3), which is expressed in a subset of spermatogonia. FGFR3-activating mutations have been identified in spermatocytic seminoma, thought to originate from clonal expansion of spermatogonia. In this study we aimed to characterize potential binding partners of FGFR3, and specifically its mesenchymal "c" splice isoform, in human spermatogonia. Based on expression patterns and homology to the binding site, we identified FGF1, FGF2, and FGF9 as the best candidates for natural ligands of FGFR3c in the testis. In addition, we screened non-FGF proteins and found that a proteoglycan biglycan (BGN) contains a sequence homologous to the FGFR3c binding site on FGF1, and is expressed in peritubular cells adjacent to FGFR3-expressing spermatogonia. Experiments in a cell-free system confirmed that BGN binds to FGFR3c and FGF1. In conclusion, our findings further clarify the complex regulation of FGFR3c in the human testis. We postulate that BGN is a factor secreted by peritubular cells to modulate FGFR3c signaling and thus contributes to the regulation of spermatogonial maintenance.
AB - Regulation of spermatogonial maintenance in the human testis is currently not well understood. One pathway suggested to be involved is activated by fibroblast growth factor receptor 3 (FGFR3), which is expressed in a subset of spermatogonia. FGFR3-activating mutations have been identified in spermatocytic seminoma, thought to originate from clonal expansion of spermatogonia. In this study we aimed to characterize potential binding partners of FGFR3, and specifically its mesenchymal "c" splice isoform, in human spermatogonia. Based on expression patterns and homology to the binding site, we identified FGF1, FGF2, and FGF9 as the best candidates for natural ligands of FGFR3c in the testis. In addition, we screened non-FGF proteins and found that a proteoglycan biglycan (BGN) contains a sequence homologous to the FGFR3c binding site on FGF1, and is expressed in peritubular cells adjacent to FGFR3-expressing spermatogonia. Experiments in a cell-free system confirmed that BGN binds to FGFR3c and FGF1. In conclusion, our findings further clarify the complex regulation of FGFR3c in the human testis. We postulate that BGN is a factor secreted by peritubular cells to modulate FGFR3c signaling and thus contributes to the regulation of spermatogonial maintenance.
UR - http://www.sciencedirect.com/science/article/pii/S0303720717306172?via%3Dihub
U2 - 10.1016/j.mce.2014.09.018
DO - 10.1016/j.mce.2014.09.018
M3 - Journal article
C2 - 25260943
SN - 0303-7207
VL - 399
SP - 235
EP - 243
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
ER -