Trisomy 21 alters ciliary localization of Sonic Hedgehog signaling proteins.

ABSTRACT: Trisomy 21 (T21), the cause of Down syndrome, impairs cilia-dependent Sonic Hedgehog (SHH) signaling. We investigated how T21 affects SHH signaling at the primary cilium and found that Smoothened (SMO) protein, the main effector of SHH signaling, is diminished in T21 primary cilia. Specifically, T21 cells exhibit both decreased SMO localization to cilia and reduced SMO activation. Our findings suggest that reduced ciliary SMO in T21 results from defective entry into the cilium rather than impaired transport to centrosomes. Moreover, unlike the ciliogenesis defects observed in T21, the SMO defect is not associated with increased PCNT protein abundance. We also found that other proteins critical for regulating SHH signaling, INPP5E (a positive regulator) and GPR161 (a negative regulator), sh

SUBMITTER: Schleicher WE 

PROVIDER: S-EPMC12889688 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature