Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
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SHR Neuro Krebs Kardio Lipid Stoffw Microb
Helm, JR; Bentley, M; Thorsen, KD; Wang, T; Foltz, L; Oorschot, V; Klumperman, J; Hay, JC.
Apoptosis-linked gene-2 (ALG-2)/Sec31 interactions regulate endoplasmic reticulum (ER)-to-Golgi transport: a potential effector pathway for luminal calcium.
J Biol Chem. 2014; 289(34):23609-23628
Doi: 10.1074/jbc.M114.561829
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- Führende Autor*innen der Med Uni Graz
- Hay Jesse
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- Abstract:
- Luminal calcium released from secretory organelles has been suggested to play a regulatory role in vesicle transport at several steps in the secretory pathway; however, its functional roles and effector pathways have not been elucidated. Here we demonstrate for the first time that specific luminal calcium depletion leads to a significant decrease in endoplasmic reticulum (ER)-to-Golgi transport rates in intact cells. Ultrastructural analysis revealed that luminal calcium depletion is accompanied by increased accumulation of intermediate compartment proteins in COPII buds and clusters of unfused COPII vesicles at ER exit sites. Furthermore, we present several lines of evidence suggesting that luminal calcium affected transport at least in part through calcium-dependent interactions between apoptosis-linked gene-2 (ALG-2) and the Sec31A proline-rich region: 1) targeted disruption of ALG-2/Sec31A interactions caused severe defects in ER-to-Golgi transport in intact cells; 2) effects of luminal calcium and ALG-2/Sec31A interactions on transport mutually required each other; and 3) Sec31A function in transport required luminal calcium. Morphological phenotypes of disrupted ALG-2/Sec31A interactions were characterized. We found that ALG-2/Sec31A interactions were not required for the localization of Sec31A to ER exit sites per se but appeared to acutely regulate the stability and trafficking of the cargo receptor p24 and the distribution of the vesicle tether protein p115. These results represent the first outline of a mechanism that connects luminal calcium to specific protein interactions regulating vesicle trafficking machinery. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.
- Find related publications in this database (using NLM MeSH Indexing)
- Apoptosis Regulatory Proteins - genetics
- Apoptosis Regulatory Proteins - metabolism
- Biological Transport -
- Calcium - metabolism
- Calcium-Binding Proteins - genetics
- Calcium-Binding Proteins - metabolism
- Cell Line -
- Endoplasmic Reticulum - metabolism
- Golgi Apparatus - metabolism
- Humans -
- Microscopy, Fluorescence -
- Protein Binding -
- RNA, Small Interfering - genetics
- Vesicular Transport Proteins - genetics
- Vesicular Transport Proteins - metabolism
- Find related publications in this database (Keywords)
- Calcium-binding Protein
- Endoplasmic Reticulum (ER)
- Golgi
- Membrane Trafficking
- Secretion
- Vesicles
- Endoplasmic Reticulum to Golgi Transport