The R-spondin family of proteins: Emerging regulators of WNT signaling

Recently, the R-spondin (RSPO) family of proteins has emerged as important regulators of WNT signaling. Considering the wide spectrum of WNT signaling functions in normal biological processes and disease conditions, there has been a significantly growing interest in understanding the functional roles of RSPOs in multiple biological processes and determining the molecular mechanisms by which RSPOs regulate the WNT signaling pathway. Recent advances in the RSPO research field revealed some of the in vivo functions of RSPOs and provided new information regarding the mechanistic roles of RSPO activity in regulation of WNT signaling. Herein, we review recent progress in RSPO research with an emphasis on signaling mechanisms and biological functions.

► R-spondins are a family of cysteine-rich, thrombospondin type I repeat containing proteins that activate both the WNT/β-catenin and WNT/PCP pathways. ► The LGR4/5/6 proteins act as receptors for R-spondins. ► R-spondins potentiate WNT ligand activity as either coactivators or inhibitors of WNT signaling receptor degradation. ► The R-spondin gene mutations are associated with human genetic diseases and cancer. ► The R-spondin genes are essential for various developmental processes in mice.