Emerging Mechanisms and Roles for Asymmetric Cytokinesis.

Cytokinesis completes cell division by physically separating the contents of the mother cell between the two daughter cells. This event requires the highly coordinated reorganization of the cytoskeleton within a precise window of time to ensure faithful genomic segregation. In addition, recent progress in the field highlighted the importance of cytokinesis in providing particularly important cues in the context of multicellular tissues. The organization of the cytokinetic machinery and the asymmetric localization or inheritance of the midbody remnants is critical to define the spatial distribution of mechanical and biochemical signals. After a brief overview of the conserved steps of animal cytokinesis, we review the mechanisms controlling polarized cytokinesis focusing on the challenges of epithelial cytokinesis. Finally, we discuss the significance of these asymmetries in defining embryonic body axes, determining cell fate, and ensuring the correct propagation of epithelial organization during proliferation.

Novel SPG3A and SPG4 mutations in dominant spastic paraplegia families.

OBJECTIVES: The hereditary spastic paraplegias (HSP) are a genetically and clinically heterogeneous group of neurodegenerative disorders, mainly characterized by a progressive spasticity and weakness of the lower limbs. Mutations in the SPG4 and SPG3A genes are responsible for approximately 50% of autosomal dominant HSP. To genetically diagnose the Portuguese families with HSP, mutation analysis was performed for the SPG4 and SPG3A genes. PATIENTS AND METHODS: Analysis was performed by polymerase chain reaction, followed by denaturing high performance liquid chromatography (DHPLC), in 61 autosomal dominant (AD)-HSP families and 19 unrelated patients without family history. RESULTS: Ten novel mutations were identified: one in the SPG3A and nine in the SPG4 genes; three known mutations in the SPG4 were also found. Most of the novel mutations were frameshift or nonsense (80%), resulting in a dysfunctional protein. CONCLUSIONS: The SPG4 and SPG3A analysis allowed the identification of 10 novel mutations and the genetic diagnosis of approximately a quarter of our AD-HSP families.