RT Journal Article
SR Electronic
T1 PEDF-Rpsa-Itga6 signaling regulates cortical neuronal morphogenesis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.01.06.895672
DO 10.1101/2020.01.06.895672
A1 Sara M. Blazejewski
A1 Sarah A. Bennison
A1 Ngoc T. Ha
A1 Xiaonan Liu
A1 Trevor H. Smith
A1 Kimberly J. Dougherty
A1 Kazuhito Toyo-oka
YR 2020
UL http://biorxiv.org/content/early/2020/05/30/2020.01.06.895672.abstract
AB Neuromorphological defects underlie neurodevelopmental disorders and functional defects. We identified a function for ribosomal protein SA (Rpsa) in regulating neuromorphogenesis using in utero electroporation to knockdown Rpsa, which results in apical dendrite misorientation, fewer/shorter extensions with decreased arborization, and decreased spine density with altered spine morphology. We investigated Rpsa’s ligand, pigment epithelium-derived factor (PEDF), and interacting partner on the plasma membrane, Integrin subunit α6 (Itga6). Rpsa, PEDF, and Itga6 knockdown cause similar phenotypes, with Rpsa and Itga6 overexpression rescuing morphological defects in PEDF deficient neurons in vivo. Additionally, Itga6 overexpression increases and stabilizes Rpsa expression on the plasma membrane by preventing ubiquitination of Rpsa. GCaMP6s was used to functionally analyze Rpsa knockdown via ex vivo calcium imaging. Rpsa deficient neurons showed less fluctuation in fluorescence intensity, suggesting defective sub-threshold calcium signaling. Our study identifies a role for PEDF-Rpsa-Itga6 signaling in neuromorphogenesis, thus implicating these molecules in the etiology of neurodevelopmental disorders and identifying them as potential therapeutic candidates.Competing Interest StatementThe authors have declared no competing interest.