title: Polyglutamylated Tubulin Binding Protein C1orf96/CSAP Is Involved in Microtubule Stabilization in Mitotic Spindles.
abstract: The centrosome-associated C1orf96/Centriole, Cilia and Spindle-Associated Protein (CSAP) targets polyglutamylated tubulin in mitotic microtubules (MTs). Loss of CSAP causes critical defects in brain development; however, it is unclear how CSAP association with MTs affects mitosis progression. In this study, we explored the molecular mechanisms of the interaction of CSAP with mitotic spindles. Loss of CSAP caused MT instability in mitotic spindles and resulted in mislocalization of Nuclear protein that associates with the Mitotic Apparatus (NuMA), with defective MT dynamics. Thus, CSAP overload in the spindles caused extensive MT stabilization and recruitment of NuMA. Moreover, MT stabilization by CSAP led to high levels of polyglutamylation on MTs. MT depolymerization by cold or nocodazole treatment was inhibited by CSAP binding. Live-cell imaging analysis suggested that CSAP-dependent MT-stabilization led to centrosome-free MT aster formation immediately upon nuclear envelope breakdown without γ-tubulin. We therefore propose that CSAP associates with MTs around centrosomes to stabilize MTs during mitosis, ensuring proper bipolar spindle formation and maintenance.
authors.affiliation: From the Center for Innovative and Translational Medicine, Medical School, Kochi University, Kohasu, Oko-cho, Nankoku, Kochi, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Ohta
authors.affiliation: From the Center for Innovative and Translational Medicine, Medical School, Kochi University, Kohasu, Oko-cho, Nankoku, Kochi, Japan.
authors.forename: Mayako
authors.initials: M
authors.lastname: Hamada
authors.affiliation: From the Center for Innovative and Translational Medicine, Medical School, Kochi University, Kohasu, Oko-cho, Nankoku, Kochi, Japan.
authors.forename: Nobuko
authors.initials: N
authors.lastname: Sato
authors.affiliation: From the Center for Innovative and Translational Medicine, Medical School, Kochi University, Kohasu, Oko-cho, Nankoku, Kochi, Japan.
authors.forename: Iyo
authors.initials: I
authors.lastname: Toramoto
mesh_terms: D034961:Antigens, Nuclear / Q000378:metabolism; D018797:Cell Cycle Proteins; D002460:Cell Line; D002502:Centrioles / Q000378:metabolism* / Q000648:ultrastructure; D006367:HeLa Cells; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D008938:Mitosis; D034521:Nuclear Matrix-Associated Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D011099:Polyglutamic Acid / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism* / Q000648:ultrastructure; D014157:Transcription Factors; D014404:Tubulin / Q000378:metabolism
chemical_list: D034961:Antigens, Nuclear; C080632:CUX1 protein, human; D018797:Cell Cycle Proteins; D018398:Homeodomain Proteins; C050045:NUMA1 protein, human; D034521:Nuclear Matrix-Associated Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D014404:Tubulin; D011099:Polyglutamic Acid