@article{b85cd848be5e49d7b8866a85fe22ba6e,
title = "EMC is required for biogenesis of Xport-A, an essential chaperone of Rhodopsin-1 and the TRP channel",
abstract = "The ER membrane protein complex (EMC) is required for the biogenesis of a subset of tail anchored (TA) and polytopic membrane proteins, including Rhodopsin-1 (Rh1) and the TRP channel. To understand the physiological implications of EMC-dependent membrane protein biogenesis, we perform a bioinformatic identification of Drosophila TA proteins. From 254 predicted TA proteins, screening in larval eye discs identified two proteins that require EMC for their biogenesis: fan and Xport-A. Fan is required for male fertility in Drosophila and we show that EMC is also required for this process. Xport-A is essential for the biogenesis of both Rh1 and TRP, raising the possibility that disruption of Rh1 and TRP biogenesis in EMC mutants is secondary to the Xport-A defect. We show that EMC is required for Xport-A TMD membrane insertion and that EMC-independent Xport-A mutants rescue Rh1 and TRP biogenesis in EMC mutants. Finally, our work also reveals a role for Xport-A in a glycosylation-dependent triage mechanism during Rh1 biogenesis in the endoplasmic reticulum.",
author = "Gaspar, {Catarina J.} and Vieira, {L{\'i}gia C.} and Santos, {Cristiana C.} and Christianson, {John C.} and David Jakubec and Kvido Strisovsky and Colin Adrain and Domingos, {Pedro M.}",
note = "Funding Information: We thank the flow cytometry facility at IGC, the microscopy facility at IGC (more specifically Jos{\'e} Marques), the microscopy facility at ITQB-NOVA, the fly facility from IGC and the transgenics facility at Champalimaud Foundation—Centre for the Unknown. We thank the Developmental Studies Hybridoma Bank (DSHB) at the University of Iowa for antibodies and the Bloomington Drosophila Stock Centre for fly stocks. We thank Craig Montell for flies, plasmids and antibodies, Akiko Satoh for flies and antibodies, and Manu Hegde for plasmids. We also acknowledge Norbert Volkmar and Miguel Cavadas for discussions and suggestions, Nansi Jo Colley and Steve Britt for antibodies, Hugo Bellen for VAP33A antibody, Hyung Don Ryoo for UAS-Rh1 flies and hid antibody, Stephen High for cells and Paulo Navarro Costa for flies. We thank Sebastien Alfaiate for help with figure design. The project leading to these results was funded by {\textquoteleft}la Caixa{\textquoteright} Foundation, under the agreement <LCF/PR/HR17/ 52150018>. Funding Information: We thank the flow cytometry facility at IGC, the microscopy facility at IGC (more specifically Jos{\'e} Marques), the microscopy facility at ITQB‐NOVA, the fly facility from IGC and the transgenics facility at Champalimaud Foundation—Centre for the Unknown. We thank the Developmental Studies Hybridoma Bank (DSHB) at the University of Iowa for antibodies and the Bloomington Drosophila Stock Centre for fly stocks. We thank Craig Montell for flies, plasmids and antibodies, Akiko Satoh for flies and antibodies, and Manu Hegde for plasmids. We also acknowledge Norbert Volkmar and Miguel Cavadas for discussions and suggestions, Nansi Jo Colley and Steve Britt for antibodies, Hugo Bellen for VAP33A antibody, Hyung Don Ryoo for UAS‐Rh1 flies and hid antibody, Stephen High for cells and Paulo Navarro Costa for flies. We thank Sebastien Alfaiate for help with figure design. The project leading to these results was funded by {\textquoteleft}la Caixa{\textquoteright} Foundation, under the agreement . Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2022",
month = jan,
day = "5",
doi = "10.15252/embr.202153210",
language = "English",
volume = "23",
journal = "Embo Reports",
issn = "1469-221X",
publisher = "Nature Publishing Group",
number = "1",
}