Drebrin as a regulator of endothelial cell-cell and cell-matrix contact
Final Report Abstract
In this project, we investigated the roles of the actin-binding protein drebrin on the regulation of endothelial cytoskeletal regulation. Based on previous findings that drebrin anchors the adherens junction protein nectin-1 to the subcortical cytoskeleton, we could identify Rab5abased endocytosis as a counter-regulatory mechanism that enables nectin turnover at junctions. Accordingly, enhanced degradation of nectin in the absence of drebrin is abrogated by depleting Rab5a in parallel. Anongoing line of investigation concerns the role of the nucleolar phosphoprotein treacle (Treacher Collins Syndrome protein), which we identified as a novel interaction partner of drebrin. We could show by immunoprecipitation, mitochondrial retargeting and protein biochemistry that drebrin directly binds a cytoplasmic pool of treacle, through drebrin’s polyproline region interacting with treacle´s LisH domain. A nuclear localization signal in treacle´s N-terminal half could be identified in the region (aa 50-470). Moreover, nucleocytoplasmic shuttling of treacle seems to be independent of exportin 1. We are currently addressing the role of treacle and drebrin interaction during wound closure experiments, as drebrin-rich lamellipodia are also positive for treacle.
Publications
- (2017). Drebrin´s role in the maintenance of endothelial integrity. Adv. Exp. Med. Biol. 1006:347-360
Rehm, K., Linder S.
(See online at https://doi.org/10.1007/978-4-431-56550-5_21) - (2021): Nectin stabilization at adherens junctions is counteracted by Rab5a-dependent endocytosis. In: European journal of cell biology 100 (7-8), S. 151184
Vrenken, K., Klose, M., Linder, S., Rehm, K.
(See online at https://doi.org/10.1016/j.ejcb.2021.151184)
