【摘 要】
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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 identifie
【机 构】
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Department of Pathology,New York University Cancer Institute,New York University School of Medicine,
论文部分内容阅读
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.
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