KANK: a novel EB1 interactor and drosophila orthologue of a conserved tumour suppressor

Abstract

The conserved human protein KANK1 has been identified as a tumour suppressor and its expression is down-regulated in several tumour types. Roles for this protein in actin regulation, cell migration and cell polarity have been documented in cultured mammalian cells. In C. elegans the KANK1 orthologue, VAB-19, is required for normal development as it helps stabilise attachment structures between muscle and epidermal cells. Despite these studies, the precise cellular role of KANK remains elusive. It was found that the Drosophila KANK orthologue binds directly to EB1, a crucial regulator of microtubule plus-end dynamics. I aimed to determine the role of KANK with respect to this indirect microtubule interaction using Drosophila. I identified residues which mediate the interaction between KANK and EB1, and showed they are essential for localisation of KANK to microtubule plus-ends in Drosophila culture cells. I found that KANK expression increases during embryogenesis and peaks in the late embryonic development when KANK is shown to localise to sites of attachment between muscle and epidermal cells. This suggests a role for the protein in stabilisation of muscle attachment during embryonic development, a process previously shown to require EB1. I generated a KANK deletion mutant and found they are viable and fertile but show a mild neuronal phenotype, specifically early branching of the neurons and less organised neuron bundles. My results suggest previously unknown roles for KANK in myogenesis and neurogenesis in Drosophila embryogenesis.