Scientific Publications

A haploid genetic screen identifies the major facilitator domain containing 2A (MFSD2A) transporter as a key mediator in the response to tunicamycin.

Publication TypeJournal Article
AuthorsReiling, JH, Clish CB, Carette JE, Varadarajan M., Brummelkamp TR, and Sabatini DM
AbstractTunicamycin (TM) inhibits eukaryotic asparagine-linked glycosylation, protein palmitoylation, ganglioside production, proteoglycan synthesis, 3-hydroxy-3-methylglutaryl coenzyme-A reductase activity, and cell wall biosynthesis in bacteria. Treatment of cells with TM elicits endoplasmic reticulum stress and activates the unfolded protein response. Although widely used in laboratory settings for many years, it is unknown how TM enters cells. Here, we identify in an unbiased genetic screen a transporter of the major facilitator superfamily, major facilitator domain containing 2A (MFSD2A), as a critical mediator of TM toxicity. Cells without MFSD2A are TM-resistant, whereas MFSD2A-overexpressing cells are hypersensitive. Hypersensitivity is associated with increased cellular TM uptake concomitant with an enhanced endoplasmic reticulum stress response. Furthermore, MFSD2A mutant analysis reveals an important function of the C terminus for correct intracellular localization and protein stability, and it identifies transmembrane helical amino acid residues essential for mediating TM sensitivity. Overall, our data uncover a critical role for MFSD2A by acting as a putative TM transporter at the plasma membrane.
Year of Publication2011
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue29
Pages11756-65
Date Published (YYYY/MM/DD)2011/07/19
ISSN Number0027-8424
DOI10.1073/pnas.1018098108
PubMedhttp://www.ncbi.nlm.nih.gov/pubmed/21677192?dopt=Abstract