Autosomal recessive variants in TUBGCP2 alter the γ-tubulin ring complex leading to neurodevelopmental disease
Serdal Güngör, Yavuz Oktay, Semra Hız, Álvaro Aranguren‐Ibáñez, İpek Polat Kalafatcilar, Ahmet Yaramış, Ezgi Karaca, Uluç Yiş, Ece Sönmezler, Burcu Ekinci, Mahmut Aslan, Elmasnur Yilmaz, Bilge Özgör, B. Sunitha, Nora Szabó, Steven Laurie, Sergi Beltrán, Daniel G. MacArthur, Denisa Hathazi, Ana Töpf, Andreas Roos, Hanns Lochmüller, Isabelle Vernos, Rita Horváth
Abstract
encoding the γ-tubulin complex 2 (GCP2) protein. This variant is predicted to disrupt the electrostatic interaction of GCP2 with GCP3. In primary fibroblasts carrying the variant, we observed a faint delocalization of γ-tubulin during the cell cycle but normal GCP2 protein levels. Through mass spectrometry, we observed dysregulation of multiple proteins involved in the assembly and organization of the cytoskeleton and the extracellular matrix, controlling cellular adhesion and of proteins crucial for neuronal homeostasis including axon guidance. In summary, our functional and proteomic studies link TUBGCP2 and the γ-tubulin complex to the development of the central nervous system in humans.