Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Rayl, M; Truitt, M; Held, A; Sargeant, J; Thorsen, K; Hay, JC.
Penta-EF-Hand Protein Peflin Is a Negative Regulator of ER-To-Golgi Transport.
PLoS One. 2016; 11(6):e0157227-e0157227
Doi: 10.1371/journal.pone.0157227
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Führende Autor*innen der Med Uni Graz
- Hay Jesse
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- Luminal calcium regulates vesicle transport early in the secretory pathway. In ER-to-Golgi transport, depletion of luminal calcium leads to significantly reduced transport and a buildup of budding and newly budded COPII vesicles and vesicle proteins. Effects of luminal calcium on transport may be mediated by cytoplasmic calcium sensors near ER exits sites (ERES). The penta-EF-hand (PEF) protein apoptosis-linked gene 2 (ALG-2) stabilizes sec31A at ER exit sites (ERES) and promotes the assembly of inner and outer shell COPII components. However, in vitro and intact cell approaches have not determined whether ALG-2 is a negative or positive regulator, or a regulator at all, under basal physiological conditions. ALG-2 interacts with another PEF protein, peflin, to form cytosolic heterodimers that dissociate in response to calcium. However, a biological function for peflin has not been demonstrated and whether peflin and the ALG-2/peflin interaction modulates transport has not been investigated. Using an intact, single cell, morphological assay for ER-to-Golgi transport in normal rat kidney (NRK) cells, we found that depletion of peflin using siRNA resulted in significantly faster transport of the membrane cargo VSV-G. Double depletion of peflin and ALG-2 blocked the increased transport resulting from peflin depletion, demonstrating a role for ALG-2 in the increased transport. Furthermore, peflin depletion caused increased targeting of ALG-2 to ERES and increased ALG-2/sec31A interactions, suggesting that peflin may normally inhibit transport by preventing ALG-2/sec31A interactions. This work identifies for the first time a clear steady state role for a PEF protein in ER-to-Golgi transport-peflin is a negative regulator of transport.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Apoptosis Regulatory Proteins - genetics
- Apoptosis Regulatory Proteins - metabolism
- Biological Transport, Active - physiology
- CHO Cells -
- COP-Coated Vesicles - genetics
- COP-Coated Vesicles - metabolism
- Calcium-Binding Proteins - genetics
- Calcium-Binding Proteins - metabolism
- Cricetinae -
- Cricetulus -
- Endoplasmic Reticulum - genetics
- Endoplasmic Reticulum - metabolism
- Golgi Apparatus - genetics
- Humans -
- Rats -