Efficient secretion of small proteins in mammalian cells relies on Sec62-dependent posttranslational translocation

Article Article scientifique Article Efficient secretion of small proteins in mammalian cells relies on Sec62-dependent posttranslational translocation eng 2012-05-30 2012-07-15 author Lakkaraju Asvin Krishna Kumar Department of Cell Biology, Sciences III, University of Geneva, CH-1211 Geneva 4, Switzerland 589690 author Thankappan Ratheeshkumar Department of Cell Biology, Sciences III, University of Geneva, CH-1211 Geneva 4, Switzerland 679211 author Mary Camille Department of Cell Biology, Sciences III, University of Geneva, CH-1211 Geneva 4, Switzerland 563441 Département de physiologie cellulaire et métabolisme (PHYME) author Garrison Jennifer L. Howard Hughes Medical Institute, Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158 author Taunton Jack Howard Hughes Medical Institute, Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158 author Strub Katharina Department of Cell Biology, Sciences III, University of Geneva, CH-1211 Geneva 4, Switzerland 27661 2712-2722 10.1091/mbc.e12-03-0228 22648169 1059-1524 PMC3395660 https://www.molbiolcell.org/doi/10.1091/mbc.e12-03-0228 <p>Mammalian cells secrete a large number of small proteins, but their mode of translocation into the endoplasmic reticulum is not fully understood. Cotranslational translocation was expected to be inefficient due to the small time window for signal sequence recognition by the signal recognition particle (SRP). Impairing the SRP pathway and reducing cellular levels of the translocon component Sec62 by RNA interference, we found an alternate, Sec62-dependent translocation path in mammalian cells required for the efficient translocation of small proteins with N-terminal signal sequences. The Sec62-dependent translocation occurs posttranslationally via the Sec61 translocon and requires ATP. We classified preproteins into three groups: 1) those that comprise ≤100 amino acids are strongly dependent on Sec62 for efficient translocation; 2) those in the size range of 120–160 amino acids use the SRP pathway, albeit inefficiently, and therefore rely on Sec62 for efficient translocation; and 3) those larger than 160 amino acids depend on the SRP pathway to preserve a transient translocation competence independent of Sec62. Thus, unlike in yeast, the Sec62-dependent translocation pathway in mammalian cells serves mainly as a fail-safe mechanism to ensure efficient secretion of small proteins and provides cells with an opportunity to regulate secretion of small proteins independent of the SRP pathway.</p> Dewey 570 46 Département de biologie cellulaire 165 false Molecular biology of the cell 23 14 f628fcda-2c5a-4e3a-8661-639bc345ecd6 Article (Published version) Public mbc.e12-03-0228.pdf 2450448 application/pdf CC BY-NC-SA-3.0 ef96daddd8d6386476ecb76894cff770668a465a22b78d68a03a6f09340a5712 openAccess Faculté des sciences / Section de biologie / Département de biologie cellulaire

Title	Published in	Year	Views	Downloads

Cotranslational vs. posttranslational protein import into the mammalian endoplasmic reticulum		2014	751	3
Efficient secretion of small proteins in mammalian cells relies on Sec62-dependent posttranslational translocation	Molecular biology of the cell	2012	72	180

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Thankappan, Ratheeshkumar