An alternative pathway for membrane protein biogenesis at the endoplasmic reticulum
AuthorsO’Keefe, Sarah; orcid: 0000-0002-1744-0198; email: firstname.lastname@example.org
Zong, Guanghui; orcid: 0000-0002-7335-039X
Duah, Kwabena B.
Andrews, Lauren E.
Shi, Wei Q.; orcid: 0000-0001-5453-1753
High, Stephen; orcid: 0000-0002-4532-8152; email: email@example.com
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AbstractAbstract: The heterotrimeric Sec61 complex is a major site for the biogenesis of transmembrane proteins (TMPs), accepting nascent TMP precursors that are targeted to the endoplasmic reticulum (ER) by the signal recognition particle (SRP). Unlike most single-spanning membrane proteins, the integration of type III TMPs is completely resistant to small molecule inhibitors of the Sec61 translocon. Using siRNA-mediated depletion of specific ER components, in combination with the potent Sec61 inhibitor ipomoeassin F (Ipom-F), we show that type III TMPs utilise a distinct pathway for membrane integration at the ER. Hence, following SRP-mediated delivery to the ER, type III TMPs can uniquely access the membrane insertase activity of the ER membrane complex (EMC) via a mechanism that is facilitated by the Sec61 translocon. This alternative EMC-mediated insertion pathway allows type III TMPs to bypass the Ipom-F-mediated blockade of membrane integration that is seen with obligate Sec61 clients.
CitationCommunications Biology, volume 4, issue 1, page 828
PublisherNature Publishing Group UK
DescriptionFrom Springer Nature via Jisc Publications Router
History: received 2020-11-18, accepted 2021-06-17, registration 2021-06-18, pub-electronic 2021-07-01, online 2021-07-01, collection 2021-12
Publication status: Published
Funder: Wellcome Trust (Wellcome); doi: https://doi.org/10.13039/100010269; Grant(s): 204957/Z/16/Z
Funder: Ball State University (Ball State); doi: https://doi.org/10.13039/100008326; Grant(s): Provost Startup Award