Amita Arora (Finland)
Minerva Foundation Institute for Medical Research
Minerva Foundation Institute for Medical Research
I started my career studying insulin signaling and insulin resistance in skeletal muscle cells, neuronal cells and adipocytes under the supervision of Professor Chinmoy Sankar Dey at Indian Institute of Technology (IIT) Delhi, India. My doctoral thesis focused on understanding how SIRT2 regulates insulin signaling in these cell types. In 2018, I moved to Finland as a postdoctoral fellow to work with Professor Vesa Olkkonen at Minerva Foundation Institute for Medical Research, Helsinki. Here, I am involved in understanding the role of membrane contact site (MCS) proteins in endothelial cell function and angiogenesis per se. As a part of this study, we have used primary endothelial cells and knockout mice model to elucidate the role of Protrudin, an endoplasmic reticulum-endosome MCS protein in vascular progression and angiogenesis.

Presenter of 1 Presentation

 Conference Calendar

ROLE OF PROTRUDIN IN ENDOTHELIAL CELL FUNCTION

Session Name
0640 - Endothelial cell biology in atherosclerosis (ID 6)
Session Type
Workshop - Pathogenesis, vascular biology
Date
Tue, 24.05.2022
Session Time
15:45 - 17:15
Room
Anitschkow - Silver Plenary hall
Presenter
Lecture Time
16:15 - 16:25

Abstract

Background and Aims

During angiogenesis, endothelial cells form protrusive sprouts and migrate towards the angiogenic stimulus. Protrudin/ZFYVE27, an endoplasmic reticulum (ER)-anchored protein, is essential for neurite outgrowth. It also promotes invadopodia formation and invasion of breast cancer cells. However, the role of Protrudin in endothelial cell function is not known. In the present study we investigate the role of Protrudin in endothelial cell migration and angiogenesis.

Methods

Various methodologies like in vitro tube formation assay, RNA sequencing, western immunoblotting and confocal imaging were adopted to elucidate the role of Protrudin in endothelial cells.

Results

Our results demonstrate that Protrudin promotes angiogenic tube formation in primary endothelial cells, Human umbilical vein endothelial cells (HUVECs). Analysis and validation of RNA sequencing data revealed cell migration as a prominent cellular function affected in HUVECs upon Protrudin knockdown. Furthermore, knockdown of Protrudin inhibits focal adhesion kinase (FAK) activation in HUVECs and human aortic endothelial cells (HAECs). This is associated with loss of polarized FAK distribution. Protrudin inhibition results in perinuclear accumulation of mTOR and inhibits S6K activation. Furthermore, C57Bl/6J mice with global deletion of Protrudin demonstrate reduced retinal vascular progression at post-natal day 7 (n=5, *p<0.05).

Conclusions

Overall, our results demonstrate that Protrudin regulates FAK and mTOR/S6K signaling pathways in endothelial cells and provide evidence for a key role of Protrudin in angiogenesis in vitro and in vivo. As Protrudin has been previously known to promote cancer cell invasion, it will be intriguing to further study its role in tumor angiogenesis and neovascularization of arthesclerotic plaques.

Hide