Abstract
Hsp70/Hsp90-organizing protein (HOP) is a member of the co-chaperone family, which directly binds to chaperones to regulate their activities. The participation of HOP in cell motility and endothelial cell functions remains largely unknown. In this study, we demonstrate that HOP is critically involved in endothelial cell migration and angiogenesis. Tube formation and capillary sprouting experiments reveal that depletion of HOP expression significantly inhibits vessel formation from endothelial cells. Wound healing and transwell migration assays show that HOP is important for endothelial cell migration. By examination of centrosome reorientation and membrane ruffle dynamics, we find that HOP plays a crucial role in the establishment of cell polarity in response to migratory stimulus. Furthermore, our data show that HOP interacts with tubulin and colocalizes with microtubules in endothelial cells. These findings indicate HOP as a novel regulator of angiogenesis that functions through promoting vascular endothelial cell polarization and migration.
Highlights
Hsp70/Hsp90-organizing protein (HOP) is a co-chaperone protein that could directly bind to the major chaperones, Hsp70 and Hsp90, and modulate their ATPase activities [1,2,3,4]
tetratricopeptide repeat (TPR) domains are responsible for the interaction of HOP with Hsp70/Hsp90, with TPR1 for HOP binding to Hsp70 and TPR2a for HOP binding to Hsp90 [7,8]
We found that overexpression of HOP could enhance the ability of HUVECs to form tubes (Figure 1D and 1E)
Summary
Hsp70/Hsp90-organizing protein (HOP) is a co-chaperone protein that could directly bind to the major chaperones, Hsp and Hsp, and modulate their ATPase activities [1,2,3,4]. Human HOP has three tetratricopeptide repeat (TPR) domains, including TPR1, TPR2a, and TPR2b [6]. TPR domains are responsible for the interaction of HOP with Hsp70/Hsp, with TPR1 for HOP binding to Hsp and TPR2a for HOP binding to Hsp90 [7,8]. No specific ligands for the TPR2b domain have been found. HOP has non-TPR domains, including a DP repeat region and two nuclear localization signals, which render HOP to dynamically translocate between the cytoplasm and the nucleus [9,10]. HOP has been found in a number of Hsp90-independent complexes, including prion protein complex and nuclear transcription complex [11,12,13,14]
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