Rab24 modulates the last stage of mitosis.

MILITELLO, R.D.; COLOMBO M.I.

Puerto Madryn

Congreso; XLVI Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB).; 2010

Rab24 is an atypical member of the Rab GTPase family whose distribution in interphase cells has been characterized. In this study, we have analyzed the distribution of Rab24 throughout cell division. Rab24 was located at the mitotic spindle during metaphase and anaphase and in the midbody during cytokinesis. We have also observed co-localization of Rab24 with survivin, a protein involved in the regulation of mitosis. Interestingly, more than 90% of transiently transfected cells with Rab24 presented abnormal nuclear connections. These atypical connections were not observed in cells transfected with other Rab proteins. In addition, HeLa cells overexpressing Rab24, analyzed for up to 15h by time-lapse microscopy, remained connected by a chromatin bridge and did not undergo abscission. In contrast, cells overexpressing only GFP undergo a normal cytokinesis event and separate after 120 min. Furthermore, in CHO cells stably transfected with GFP-Rab24wt, we observed a large percentage of binucleated and multinucleated cells. These cells presented an extremely large size compared to stably transfected cells overexpressing GFP alone or a Rab24 mutant S67L. A marked increase in binucleated, multinucleated and multilobulated nucleus was also observed in HeLa cells silenced for Rab24. These findings suggest that Rab24 participate in a pathway involved in a late stage of the mitosis.