Tumor suppressor protein CYLD regulates morphogenesis of dendrites and spines.

Abstract

Cylindromatosis tumor suppressor protein (CYLD) was initially identified as a tumor suppressor deubiquitylating protein in familial cylindromatosis patients. Proteomic analyses using rodent brain samples revealed enrichment of CYLD in purified postsynaptic density fractions. Here, we report that CYLD regulates dendritic growth and postsynaptic differentiation in mouse hippocampal neurons. CYLD showed diffuse localization in rapidly growing dendrites, but was gradually concentrated in spines. Overexpression and knockdown of CYLD in the early stage of cultured neurons demonstrated that CYLD positively regulated dendritic growth. Phenotypes in dendritic morphogenesis induced by CYLD overexpression and knockdown could be reversed by manipulation of the critical acetylation site of α-tubulin, suggesting tubulin acetylation is a downstream pathway of CYLD-dependent dendritic growth. Overexpression and knockdown of CYLD in the later stage of cultured neurons revealed that CYLD promoted formation of postsynaptic spines. Influence of CYLD on spines was not affected by co-expression of acetylation mutant forms of α-tubulin, indicating that CYLD regulates dendritic growth and spine formation through different molecular mechanisms. Analyses with the truncated and mutated forms of CYLD demonstrated that the first microtubule-binding domain of CYLD was critical for spine formation. These results suggest important roles of CYLD in sequential promotion of dendritic growth and postsynaptic spine maturation.

• Authors: Jun Li, Yoko Sekine-Aizawa, Saman Ebrahimi, Shinji Tanaka, Shigeo Okabe
• Journal: The European journal of neuroscience (Eur J Neurosci) Vol. 50 Issue 4 Pg. 2722-2739 (08 2019) ISSN: 1460-9568 [Electronic] France
• PMID: 31001844 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Chemical References

• Tubulin
• CYLD protein, mouse
• Deubiquitinating Enzyme CYLD

Topics

• Acetylation
• Animals
• Cell Differentiation
• Cells, Cultured
• Dendrites (ultrastructure)
• Dendritic Spines (ultrastructure)
• Deubiquitinating Enzyme CYLD (genetics, physiology)
• Gene Knockdown Techniques
• Hippocampus (ultrastructure)
• Mice
• Microtubules (metabolism)
• Morphogenesis (genetics)
• Primary Cell Culture
• Protein Binding
• Tubulin (metabolism)