TD-60 links RalA GTPase function to the CPC in mitosis

TD-60 (also known as RCC2) is a highly conserved protein that structurally resembles the Ran guanine exchange factor (GEF) RCC1, but has not previously been shown to have GEF activity. TD-60 has a typical chromosomal passenger complex (CPC) distribution in mitotic cells, but associates with integrin complexes and is involved in cell motility during interphase. Here we show that TD-60 exhibits GEF activity, in vitro and in cells, for the small GTPase RalA. TD-60 or RalA depletion causes spindle abnormalities in prometaphase associated with abnormal centromeric accumulation of CPC components. TD-60 and RalA apparently work together to contribute to the regulation of kinetochore–microtubule interactions in early mitosis. Importantly, several mitotic phenotypes caused by TD-60 depletion are reverted by the expression of a GTP-locked mutant, RalA (Q72L). The demonstration that a small GTPase participates in the regulation of the CPC reveals a level of mitotic regulation not suspected in previous studies

Rhabdoviruses as Vaccine Vectors for Veterinary Pathogens

Rhabdoviruses are simple RNA viruses, which are open to genetic manipulation. Recombinant vector vaccines based on vesicular stomatitis virus (VSV) or rabies virus (RABV) are capable of inducing strong and protective immune responses in animals and humans as exemplified by the VSV-based Ebola virus vaccine. As several rhabdoviruses are harmful for animals and/or humans, the recombinant vector vaccine derived from them needs to be properly attenuated. Single-cycle vector vaccines and interferon-stimulating viruses represent attractive strategies to achieve attenuation. VSV and RABV are notifiable Office International des Epizooties (OIE)-listed pathogens, and this has impeded their general use in the veterinary field. However, vector vaccines based on different non-notifiable rhabdoviruses may represent an attractive alternative