Inseparable/IER3IP1are essential for cytokinesis inDrosophilaneuroblast and human cells

Abstract

AbstractTo unveil the molecular players that maintain neural stem cell homeostasis, we conducted a genetic screen inDrosophilaand isolated an uncharacterized gene that we namedInseparable(Insep).Insepis theDrosophilahomologue of humanIER3IP1, a gene associated with Microcephaly, Epilepsy, and Neonatal Diabetes Syndrome (MEDS-1). We show thatInseploss leads to early larval lethality with small brains and these phenotypes can be rescued by expressing IER3IP1 indicating that their biological function is conserved through evolution. TheInsepdeficient neuroblasts fail to complete cytokinesis and show excessive accumulation of Rab11 vesicles in the cytoplasm. Similarly,IER3IP1depletion in human cells leads to cytokinesis failure and accumulation of Rab11 vesicles. Insep and IER3IP1 localize to Rab11 vesicles and interact with Rab11. The pathogenic mutations in IER3IP1 perturb its localization to Rab11 vesicles and interaction with Rab11. These results suggest that Insep and IER3IP1 work along with Rab11 and may regulate fusion of Rab11 vesicles to the advancing furrow during cytokinesis.