한빛사논문 | BRIC

한빛사 논문

조회552

University of Texas Southwestern Medical Center

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Cell Reports, Vol 42, Issue 4, 25 April 2023, 112311 | https://doi.org/10.1016/j.celrep.2023.112311 Topological regulation of a transmembrane protein by luminal-to-cytosolic retrotranslocation of glycosylated sequence

Jingcheng Wang ^1,2, Sungwon Han ^1,2, Jin Ye ^1,3

¹Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
²These authors contributed equally
³Lead contact

Corresponding author: Jin Ye

Abstract

Transmembrane proteins must adopt proper topology to perform their functions. We previously demonstrated that ceramide regulates TM4SF20 (transmembrane 4 L6 family 20) by altering the topology of the transmembrane protein, but the underlying mechanism remains obscure. Here we report that TM4SF20 is synthesized in the endoplasmic reticulum (ER) with a cytosolic C terminus and a luminal loop before the last transmembrane helix where N132, N148, and N163 are glycosylated. In the absence of ceramide, the sequence surrounding glycosylated N163 but not N132 is retrotranslocated from lumen to cytosol independent of ER-associated degradation. Accompanying this retrotranslocation, the C terminus of the protein is relocated from cytosol to lumen. Ceramide delays the retrotranslocation process, causing accumulation of the protein that is originally synthesized. Our findings suggest that N-linked glycans, although synthesized in the lumens, may be exposed to cytosol through retrotranslocation, a reaction that may play a crucial role in topological regulation of transmembrane proteins.

논문정보

형식Research article
게재일2023년 04월 (BRIC 등록일 2023-05-14)
연구진국외 연구진
분야 생명과학 > 세포생물학

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