Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Bentley, M; Nycz, DC; Joglekar, A; Fertschai, I; Malli, R; Graier, WF; Hay, JC.
Vesicular calcium regulates coat retention, fusogenicity, and size of pre-Golgi intermediates.
Mol Biol Cell. 2010; 21(6):1033-1046
Doi: 10.1091/mbc.E09-10-0914
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- Führende Autor*innen der Med Uni Graz
- Hay Jesse
- Co-Autor*innen der Med Uni Graz
- Fertschai Ismene
- Graier Wolfgang
- Malli Roland
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- Abstract:
- The significance and extent of Ca(2+) regulation of the biosynthetic secretory pathway have been difficult to establish, and our knowledge of regulatory relationships integrating Ca(2+) with vesicle coats and function is rudimentary. Here, we investigated potential roles and mechanisms of luminal Ca(2+) in the early secretory pathway. Specific depletion of luminal Ca(2+) in living normal rat kidney cells using cyclopiazonic acid (CPA) resulted in the extreme expansion of vesicular tubular cluster (VTC) elements. Consistent with this, a suppressive role for vesicle-associated Ca(2+) in COPII vesicle homotypic fusion was demonstrated in vitro using Ca(2+) chelators. The EF-hand-containing protein apoptosis-linked gene 2 (ALG-2), previously implicated in the stabilization of sec31 at endoplasmic reticulum exit sites, inhibited COPII vesicle fusion in a Ca(2+)-requiring manner, suggesting that ALG-2 may be a sensor for the effects of vesicular Ca(2+) on homotypic fusion. Immunoisolation established that Ca(2+) chelation inhibits and ALG-2 specifically favors residual retention of the COPII outer shell protein sec31 on pre-Golgi fusion intermediates. We conclude that vesicle-associated Ca(2+), acting through ALG-2, favors the retention of residual coat molecules that seem to suppress membrane fusion. We propose that in cells, these Ca(2+)-dependent mechanisms temporally regulate COPII vesicle interactions, VTC biogenesis, cargo sorting, and VTC maturation.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- COP-Coated Vesicles - metabolism
- COP-Coated Vesicles - ultrastructure
- Calcium - metabolism
- Calcium-Binding Proteins - metabolism
- Cells, Cultured -
- Chelating Agents - chemistry
- Chelating Agents - metabolism
- Egtazic Acid - analogs & derivatives
- Egtazic Acid - chemistry
- Egtazic Acid - metabolism
- Golgi Apparatus - metabolism
- Golgi Apparatus - ultrastructure
- Membrane Fusion - physiology
- Molecular Structure -
- Rats -
- Secretory Pathway - physiology