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Comment
. 2011 Jul 19;108(29):11731-2.
doi: 10.1073/pnas.1109035108. Epub 2011 Jul 6.

Knocking out the door to tunicamycin entry

Michael C Bassik  1 , Martin Kampmann
Affiliations
Comment

Knocking out the door to tunicamycin entry

Michael C Bassik et al. Proc Natl Acad Sci U S A. .
No abstract available

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.
Fig. 1.
Model for tunicamycin uptake through MFSD2A. (A) Results by Reiling et al. (8) suggest that the human MFSD2A gene encodes a plasma membrane transporter that mediates uptake of the antibiotic tunicamycin (TM; red diamonds) into cells. After it is in the cytoplasm, TM inhibits DPAGT1, a protein required for N-linked protein glycosylation in the ER. Inhibition of N-linked protein glycosylation triggers the unfolded protein response and eventually, leads to apoptosis. (B) Reiling et al. (8) identify MFSD2A in a TM resistance screen using insertional mutagenesis in a haploid human cell line. MFSD2A-depleted cells are TM-resistant. Genetic interaction studies reveal that MFSD2A acts upstream of DPAGT1 and the ER chaperone GRP78. Depletion of DPAGT1 or GRP78 sensitizes WT cells to TM; this effect is blocked in MFSD2A-depleted cells. (C) Overexpression of MFSD2A enhances TM uptake and sensitivity, increasing the amount of unglycosylated, misfolded proteins.
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