RESUMO
XMAP215/Dis1 family proteins are potent microtubule polymerases, critical for mitotic spindle structure and dynamics. While microtubule polymerase activity is driven by an N-terminal tumor overexpressed gene (TOG) domain array, proper cellular localization is a requisite for full activity and is mediated by a C-terminal domain. Structural insight into the C-terminal domain's architecture and localization mechanism remain outstanding. We present the crystal structure of the Saccharomyces cerevisiae Stu2 C-terminal domain, revealing a 15-nm parallel homodimeric coiled coil. The parallel architecture of the coiled coil has mechanistic implications for the arrangement of the homodimer's N-terminal TOG domains during microtubule polymerization. The coiled coil has two spatially distinct conserved regions: CRI and CRII. Mutations in CRI and CRII perturb the distribution and localization of Stu2 along the mitotic spindle and yield defects in spindle morphology including increased frequencies of mispositioned and fragmented spindles. Collectively, these data highlight roles for the Stu2 dimerization domain as a scaffold for factor binding that optimally positions Stu2 on the mitotic spindle to promote proper spindle structure and dynamics.
Assuntos
Cinetocoros/fisiologia , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Associadas aos Microtúbulos/fisiologia , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/fisiologia , Cinetocoros/metabolismo , Microtúbulos/metabolismo , Ligação Proteica , Domínios Proteicos/fisiologia , Elementos Estruturais de Proteínas/fisiologia , Saccharomyces cerevisiae/metabolismo , Fuso Acromático/metabolismo , Fuso Acromático/fisiologia , Tubulina (Proteína)/metabolismoRESUMO
PURPOSE: To identify risk factors that may lead to the development of dysphagia after combined anterior and posterior (360°) cervical fusion surgery. METHODS: A single center, retrospective analysis of patients who had same-day, 360° fusion at Henry Ford Hospital between 2008 and 2012 was performed. Variables analyzed included demographics, medical co-morbidities, levels fused, and degree of dysphagia. RESULTS: The overall dysphagia rate was 37.7 %. Patients with dysphagia had a longer mean length of stay (p < 0.001), longer mean operative time (p < 0.001), greater intraoperative blood loss (p = 0.002), and fusion above the fourth cervical vertebra, C4, (p = 0.007). There were no differences in the rates of dysphagia when comparing patients undergoing primary or revision surgery (p = 0.554). CONCLUSION: Prolonged surgery and fusion above C4 lead to higher rates of dysphagia after 360° fusions. Prior anterior cervical fusion does not increase the risk of dysphagia development.