Trisomy 21 Represses Cilia Formation and Function.

ABSTRACT: Trisomy 21 (T21) is the most prevalent human chromosomal disorder, causing a range of cardiovascular, musculoskeletal, and neurological abnormalities. However, the cellular processes disrupted by T21 are poorly understood. Consistent with the clinical overlap between T21 and ciliopathies, we discovered that T21 disrupts cilia formation and signaling. Cilia defects arise from increased expression of Pericentrin, a centrosome scaffold and trafficking protein encoded on chromosome 21. Elevated Pericentrin is necessary and sufficient for T21 cilia defects. Pericentrin accumulates at centrosomes and dramatically in the cytoplasm surrounding centrosomes. Centrosome Pericentrin recruits more γ-tubulin and enhances microtubules, whereas cytoplasmic Pericentrin assembles into large foci that do not

SUBMITTER: Galati DF 

PROVIDER: S-EPMC6557141 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature