Arf6 Regulates Endocytosis and Angiogenesis by Promoting Filamentous Actin Assembly

Abstract

Clathrin-mediated endocytosis (CME) is a process vital to angiogenesis as well as general vascular homeostasis. In pathologies where supraphysiological growth factor signaling underlies disease etiology, such as in diabetic retinopathy and solid tumors, strategies to limit chronic growth factor signaling by way of CME have been shown to have tremendous clinical value. ADP ribosylation factor 6 (Arf6) is a small GTPase that promotes the assembly of actin necessary for CME. In its absence, growth factor signaling is greatly diminished, which has been shown to ameliorate pathological signaling input in diseased vasculature. However, it is less clear if there are bystander effects related to loss of Arf6 on angiogenic behaviors. Our goal was to provide a analysis of Arf6s function in angiogenic endothelium, focusing on its role in lumenogenesis as well as its relation to actin and CME. We found that Arf6 localized to both filamentous actin and sites of CME in 2-dimensional culture. Loss of Arf6 distorted both apicobasal polarity and reduced the total cellular filamentous actin content, and this may be the primary driver underlying gross dysmorphogenesis during angiogenic sprouting in its absence. Our findings highlight that endothelial Arf6 is a potent mediator of both actin regulation and CME.

The calcium pump PMCA4b promotes epithelial cell polarization and lumen formation

“…We show that PMCA4b colocalizes both with the wild type and a constitutively active form of Arf6, and that Arf6 inhibition interferes with PMCA4b recycling. Previous studies indicate that Arf6 plays a role in actin cytoskeleton remodeling and lumen formation in epithelial and endothelial cells (Francis et al, 2023;Milanini et al, 2018;Monteleon et al, 2012;Tushir et al, 2010;Zangari et al, 2014) that is in good agreement with our current observation demonstrating that Arf6 inhibition prevent PMCA4b-induced pre-lumen formation in 2D cell cultures (Fig. 6E, F).…”

ChatGPT in Healthcare: A Taxonomy and Systematic Review

“…By March 20, 2023, a total of 140 publications are retrieved in PubMed (https://pubmed.ncbi.nlm.nih.gov/) using the keyword ChatGPT. Among them, article written in languages other than English (e.g., French [84]), without full text access (e.g., [62]), or whose main content has little to do with (or is not specific to) either ChatGPT (e.g., [46, 104, 33, 37]) or healthcare (e.g., [97, 103, 27, 6, 39, 13, 88, 21, 66, 115, 102, 43]) are excluded. Other representative exclusions include [44, 55], which deal with CPT-3, and [56, 30, 90, 2], where the authors claimed that ChatGPT assisted with the writing of the papers or case reports, but did not provide any discussion of the appropriateness of the generated texts and how the texts were incorporated into the main content.…”