RRC ID 35969
Author Ohta S, Hamada M, Sato N, Toramoto I.
Title Polyglutamylated Tubulin Binding Protein C1orf96/CSAP Is Involved in Microtubule Stabilization in Mitotic Spindles.
Journal PLoS One
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.
Volume 10(11)
Pages e0142798
Published 2015-1-1
DOI 10.1371/journal.pone.0142798
PII PONE-D-15-23120
PMID 26562023
PMC PMC4642972
MeSH Antigens, Nuclear / metabolism Cell Cycle Proteins Cell Line Centrioles / metabolism* Centrioles / ultrastructure HeLa Cells Homeodomain Proteins / metabolism* Humans Microtubules / metabolism* Microtubules / ultrastructure Mitosis Nuclear Matrix-Associated Proteins / metabolism Nuclear Proteins / metabolism* Polyglutamic Acid / metabolism Repressor Proteins / metabolism* Spindle Apparatus / metabolism* Spindle Apparatus / ultrastructure Transcription Factors Tubulin / metabolism
IF 2.74
Times Cited 4
DNA material pDEST131NGFP126 (RDB13952) pDEST132NTrAP126 (RDB13953) pENTR4XE126 (RDB13954).