Article
- The EMBO Journal (2008) 27, 2043 - 2054
- doi:10.1038/emboj.2008.136
Published online: 24 July 2008
Subject Category:
Adaptation of endoplasmic reticulum exit sites to acute and chronic increases in cargo load
Hesso Farhan1, Matthias Weiss2, Katsuko Tani3, Randal J Kaufman4 and Hans-Peter Hauri1
- Department of Pharmacology & Neurobiology, Biozentrum, University of Basel, Basel, Switzerland
- Cellular Biophysics Group, German Cancer Research Center, Heidelberg, Germany
- School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan
- Howard Hughes Medical Institute and Department of Biological Chemistry and Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI, USA
Correspondence to:
Hans-Peter Hauri, Department of Pharmacology & Neurobiology, Biozentrum, University of Basel, Klingelbergstrasse 70, Basel CH-4056, Switzerland. Tel.: +41 61 267 22 22; Fax: +41 61 267 22 08; E-mail: Hans-Peter.Hauri@unibas.ch
Received 10 April 2008; Accepted 23 June 2008
Abstract
The biogenesis of endoplasmic reticulum (ER) exit sites (ERES) involves the formation of phosphatidylinositol-4 phosphate (PI4) and Sec16, but it is entirely unknown how ERES adapt to variations in cargo load. Here, we studied acute and chronic adaptive responses of ERES to an increase in cargo load for ER export. The acute response (within minutes) to increased cargo load stimulated ERES fusion events, leading to larger but less ERES. Silencing either PI4-kinase III
(PI4K-III) or Sec16 inhibited the acute response. Overexpression of secretory cargo for 24 h induced the unfolded protein response (UPR), upregulated COPII, and the cells formed more ERES. This chronic response was insensitive to silencing PI4K-III, but was abrogated by silencing Sec16. The UPR was required as the chronic response was absent in cells lacking inositol-requiring protein 1. Mathematical model simulations further support the notion that increasing ERES number together with COPII levels is an efficient way to enhance the secretory flux. These results indicate that chronic and acute increases in cargo load are handled differentially by ERES and are regulated by different factors.
Keywords:
- COPII,
- phosphatidylinositol-4 kinase III,
- Sec16,
- secretory pathway,
- unfolded protein response
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