We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
SLITRK5 is a negative regulator of hedgehog signaling in osteoblasts.
- Authors
Sun, Jun; Shin, Dong Yeon; Eiseman, Mark; Yallowitz, Alisha R.; Li, Na; Lalani, Sarfaraz; Li, Zan; Cung, Michelle; Bok, Seoyeon; Debnath, Shawon; Marquez, Sofia Jenia; White, Tommy E.; Khan, Abdul G.; Lorenz, Ivo C.; Shim, Jae-Hyuck; Lee, Francis S.; Xu, Ren; Greenblatt, Matthew B.
- Abstract
Hedgehog signaling is essential for bone formation, including functioning as a means for the growth plate to drive skeletal mineralization. However, the mechanisms regulating hedgehog signaling specifically in bone-forming osteoblasts are largely unknown. Here, we identified SLIT and NTRK-like protein-5(Slitrk5), a transmembrane protein with few identified functions, as a negative regulator of hedgehog signaling in osteoblasts. Slitrk5 is selectively expressed in osteoblasts and loss of Slitrk5 enhanced osteoblast differentiation in vitro and in vivo. Loss of SLITRK5 in vitro leads to increased hedgehog signaling and overexpression of SLITRK5 in osteoblasts inhibits the induction of targets downstream of hedgehog signaling. Mechanistically, SLITRK5 binds to hedgehog ligands via its extracellular domain and interacts with PTCH1 via its intracellular domain. SLITRK5 is present in the primary cilium, and loss of SLITRK5 enhances SMO ciliary enrichment upon SHH stimulation. Thus, SLITRK5 is a negative regulator of hedgehog signaling in osteoblasts that may be attractive as a therapeutic target to enhance bone formation. Hedgehog signaling is essential for bone formation. Here, the authors show that the transmembrane protein SLITRK5 is a negative regulator of hedgehog signaling in osteoblasts, suggesting it may be a potential therapeutic target to enhance bone formation.
- Subjects
OSTEOBLASTS; BONE growth; GROWTH plate; MEMBRANE proteins; CILIA &; ciliary motion; HEDGEHOG signaling proteins
- Publication
Nature Communications, 2021, Vol 12, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-021-24819-w