Regulators of tubulin polyglutamylation control nuclear shape and cilium disassembly by balancing microtubule and actin assembly

• 作者: Lei Wang Sharad C.Paudyal Yuchen Kang Mikito Owa Feng-Xia Liang Alexander Spektor Holger Knaut Irma Sánchez Brian D.Dynlacht
• 来源期刊: 细胞研究（英文版）
• 年，卷（期）: 2022,（2）
• 所属期刊栏目: ARTICLES
• 页码范围: 190-209
• 页数: 20页
• 语种: 英文

摘要

Cytoskeletal networks play an important role in regulating nuclear morphology and ciliogenesis.However,the role of microtubule (MT) post-translational modifications in nuclear shape regulation and cilium disassembly has not been explored.Here we identified a novel regulator of the tubulin polyglutamylase complex (TPGC),C11ORF49/CSTPP1,that regulates cytoskeletal organization,nuclear shape,and cilium disassembly.Mechanistically,loss of C11ORF49/CSTPP1 impacts the assembly and stability of the TPGC,which modulates long-chain polyglutamylation levels on microtubules (MTs) and thereby balances the binding of MT-associated proteins and actin nucleators.As a result,loss of TPGC leads to aberrant,enhanced assembly of MTs that penetrate the nucleus,which in turn leads to defects in nuclear shape,and disorganization of cytoplasmic actin that disrupts the YAP/TAZ pathway and cilium disassembly.Further,we showed that C11ORF49/CSTPP1-TPGC plays mechanistically distinct roles in the regulation of nuclear shape and cilium disassembly.Remarkably,disruption of C11ORF49/CSTPP1-TPGC also leads to developmental defects in vivo.Our findings point to an unanticipated nexus that links tubulin polyglutamylation with nuclear shape and ciliogenesis.