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Full-Text Articles in Medicine and Health Sciences

N-Glycosylation-Defective Splice Variants Of Neuropilin-1 Promote Metastasis By Activating Endosomal Signals, Xiuping Huang, Qing Ye, Min Chen, Aimin Li, Wenting Mi, Yuxin Fang, Yekaterina Y. Zaytseva, Kathleen L. O'Connor, Craig W. Vander Kooi, Side Liu, Qing-Bai She Aug 2019

N-Glycosylation-Defective Splice Variants Of Neuropilin-1 Promote Metastasis By Activating Endosomal Signals, Xiuping Huang, Qing Ye, Min Chen, Aimin Li, Wenting Mi, Yuxin Fang, Yekaterina Y. Zaytseva, Kathleen L. O'Connor, Craig W. Vander Kooi, Side Liu, Qing-Bai She

Markey Cancer Center Faculty Publications

Neuropilin-1 (NRP1) is an essential transmembrane receptor with a variety of cellular functions. Here, we identify two human NRP1 splice variants resulting from the skipping of exon 4 and 5, respectively, in colorectal cancer (CRC). Both NRP1 variants exhibit increased endocytosis/recycling activity and decreased levels of degradation, leading to accumulation on endosomes. This increased endocytic trafficking of the two NRP1 variants, upon HGF stimulation, is due to loss of N-glycosylation at the Asn150 or Asn261 site, respectively. Moreover, these NRP1 variants enhance interactions with the Met and β1-integrin receptors, resulting in Met/β1-integrin co-internalization and co-accumulation on endosomes. This provides persistent …


Endothelial N-Glycan Hypoglycosylation Enhances Cd16+ Monocyte Adhesion: A Role For Alpha-Mannosidases, Kellie Regal Mcdonald Jan 2019

Endothelial N-Glycan Hypoglycosylation Enhances Cd16+ Monocyte Adhesion: A Role For Alpha-Mannosidases, Kellie Regal Mcdonald

All ETDs from UAB

Monocyte extravasation through the endothelial layer is a hallmark of atherosclerotic plaque development and is mediated by heavily glycosylated surface adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1). Human monocytes have been classified into three distinct groups: classical (anti-inflammatory; CD14+/CD16-), nonclassical (patrolling; CD14+/CD16++), and intermediate (pro-inflammatory; CD14++/CD16+). The CD16+ nonclassical / intermediate monocytes have been implicated in atherosclerosis progression and their levels positively associate with adverse cardiac events. However, there is a relative lack of understanding as to whether there are distinct mechanisms that regulate CD16+ vs. CD16- monocyte adhesion to the inflamed endothelium. Our previous data identified a high-mannose …


Characterizing The Hiv-1 Envelope N-Glycan Shield, Audra Ann Hargett Jan 2019

Characterizing The Hiv-1 Envelope N-Glycan Shield, Audra Ann Hargett

All ETDs from UAB

In 2017, there was an estimated 1.8 million new HIV-1 infections worldwide. Development of an effective HIV-1 vaccine would begin to quell this global pandemic. HIV-1 envelope (Env) glycoprotein is the main vaccine candidate target due to the immune systems ability to generate broadly neutralizing antibodies (bnAbs) against Env. Approximately 90 N-glycans form a glycan shield that is the primary interface between the virus and host immune system. Key glycan motifs within the glycan shield are targets for bnAbs and are necessary for HIV-1 infectivity. Herein, we explore how naturally occurring mutations alter the glycan shield and HIV-1 Env function. …