Lack of complex type N-glycans lessens aberrant neuronal properties

Simple item page
dc.contributor.authorHall, M. Kristen
dc.contributor.authorWeidner, Douglas A.
dc.contributor.authorWhitman, Austin A.
dc.contributor.authorSchwalbe, Ruth A.
dc.date.accessioned2019-06-20T18:39:08Z
dc.date.available2019-06-20T18:39:08Z
dc.date.issued2018-06
dc.description.abstractModifications in surface glycans attached to proteins via N-acetylglucosamine-β1-Nasparagine linkage have been linked to tumor development and progression. These modifications include complex N-glycans with high levels of branching, fucose and sialic acid residues. Previously, we silenced Mgat2 in neuroblastoma (NB) cells, which halted the conversion of hybrid type N-glycans to complex type, to generate a novel cell line, NB_1 (-Mgat2). By comparing the aberrant cell properties of the NB_1(-Mgat2) cell line to the parental cell line (NB_1), we investigated the impact of eliminating complex type N-glycans on NB cell behavior. Further, the N-glycosylation pathway in the NB_1(-Mgat2) cell line was rescued by transiently transfecting cells with Mgat2, thus creating the NB_1 (-/+Mgat2) cell line. Changes in the N-glycosylation pathway were verified by enhanced binding of E-PHA and L-PHA to proteins in the rescued cell line relative to those of the NB_1(-Mgat2) cell line. Also, western blotting of total membranes from the rescued cell line ectopically expressing a voltage-gated K+ channel (Kv3.1b) revealed that N-glycans of Kv3.1b were processed to complex type. By employment of various cell lines, we demonstrated that reduction of the complex type N-glycans diminished anchorage-independent cell growth, and enhanced cell-cell interactions. Two independent cell invasion assays showed that cell invasiveness was markedly lessened by lowering the levels of complex type N-glycans while cell mobility was only slightly modified. Neurites of NB cells were shortened by the absence of complex type N-glycans. Cell proliferation was reduced in NB cells with lowered levels of complex type N-glycans which resulted from hindered progression through G1+Go phases of the cell cycle. Overall, our results illustrate that reducing the ratio of complex to hybrid types of N-glycans diminishes aberrant NB cell behavior and thereby has a suppressive effect in cell proliferation, and cell dissociation and invasion phases of NB.en_US
dc.description.sponsorshipThis work was supported in part by the Department of Biochemistry and Molecular Biology, Brody School of Medicine (to R.A.S), Wooten Laboratory grant (to R.A.S), and Open Access Publishing Support Fund at ECU (to R.A. S.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en_US
dc.identifier.citationHall, M. K., Weidner, D. A., Whitman, A. A., & Schwalbe, R. A. (2018). Lack of complex type N-glycans lessens aberrant neuronal properties. PloS One, 13(6), e0199202. doi:10.1371/journal.pone.0199202en_US
dc.identifier.doi10.1371/journal.pone.0199202 J
dc.identifier.otherPMC6002081
dc.identifier.pmid29902282en_US
dc.identifier.urihttp://hdl.handle.net/10342/7353
dc.language.isoen_USen_US
dc.relation.urihttps://www.ncbi.nlm.nih.gov/pubmed/29902282en_US
dc.titleLack of complex type N-glycans lessens aberrant neuronal propertiesen_US
dc.typeArticleen_US
ecu.journal.issue6en_US
ecu.journal.namePloS Oneen_US
ecu.journal.volume13en_US

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Lack of complex type N-glycans.pdf
Size:
8.31 MB
Format:
Adobe Portable Document Format
Description:
Main Article
Download

Collections

2018-2019 Open Access Publishing Fund