The role of the receptor complex and the cofactors in IGSF10 signaling

Immunoglobulin superfamily member 10 (IGSF10) is a large, secreted protein implicated in multiple biological and pathological processes: IGSF10 mutations are associated with hereditary delayed puberty. Low IGSF10 expression is linked to more aggressive lung and breast cancers. A frameshift mutation in IGSF10 was found in a case of a hereditary skeletal disorder, Cleidocranial Dysplasia. IGSF10 A1672T variant was found in combined pituitary hormone deficiency. However, the mechanism of action of IGSF10 is unknown. The applicant’s group identified the cell surface receptor for IGSF10 and the downstream signaling pathway regulated by IGSF10. They also identified a putative co-receptor and a secreted co-factor for IGSF10. This project is directed towards understanding the roles of the receptor complex and the cofactors in IGSF10 signaling. The successful completion of the project will uncover the molecular mechanisms and the biological roles of the novel signaling pathway mediated by IGSF10. The knowledge gained from this project will lay the foundation for understanding the physiological roles of this novel signaling pathway as well as the pathological conditions associated with the dysregulation of this pathway.