Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Thayanidhi, N; Liang, Y; Hasegawa, H; Nycz, DC; Oorschot, V; Klumperman, J; Hay, JC.
R-SNARE ykt6 resides in membrane-associated protease-resistant protein particles and modulates cell cycle progression when over-expressed.
Biol Cell. 2012; 104(7):397-417
Doi: 10.1111/boc.201100048
Web of Science
PubMed
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FullText_MUG
- Leading authors Med Uni Graz
- Hay Jesse
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- Abstract:
- The arginine-type soluble N-ethylmaleimide-sensitive factor attachment protein receptor (R-SNARE) ykt6 possesses several atypical properties including selective high expression in neurons, a lipidated C-terminus, localization to punctae that do not correspond with known endomembrane markers, a potent ability to protect the secretory pathway from alpha-synuclein over-expression and specific up-regulation in tumors. We have followed up on several of these features that together suggest nontraditional SNARE structures and functions. A significant portion of ykt6 in PC12 cells was found in a protease-resistant state suggestive of a large complex or aggregate. Other endoplasmic reticulum/Golgi SNAREs were not protease resistant, demonstrating that SNARE complexes per se did not cause protease resistance. Mutagenesis indicated that lipidation of the ykt6 C-terminus was also not involved, implicating its longin domain in particle formation. Immunogold electron microscopy revealed ykt6 labeling of ∼100 nm electron densities associated with diverse membranes. Density gradient analysis of the protease-resistant structures confirmed their tight association with membranes. Since excess ykt6 has been correlated with tumorigenesis, we tested whether ykt6 over-expression in normal rat kidney cells that normally express little ykt6 affected the cell cycle. Ykt6 over-expression was found to result in altered cell division cycles as evidenced by significantly smaller cells, a higher mitotic index and increased DNA synthesis. Mutagenesis studies dis-correlated SNARE function with the cell cycle effects; instead, the cell cycle effects correlated better with ykt6 properties related to the longin domain or particle formation. The ykt6 particles/aggregates may represent ykt6 engaged in a non-SNARE function(s) or else nonfunctional, stored and/or excess ykt6. Whether the particulate ykt6 structures represent a means of buffering the apparent proliferative activity or are in fact mechanistically related to this activity will be of future interest in neuroscience and cancer biology. Copyright © 2012 Soçiété Francaise des Microscopies and Société de Biologie Cellulaire de France.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Cell Cycle -
- Cell Membrane - metabolism
- Cell Membrane - ultrastructure
- Cell Size -
- Electrons -
- Mitotic Index -
- Models, Biological -
- Organelles - metabolism
- PC12 Cells -
- Peptide Hydrolases - metabolism
- Protein Structure, Quaternary -
- R-SNARE Proteins - chemistry
- R-SNARE Proteins - metabolism
- Rats -
- Staining and Labeling -
- Find related publications in this database (Keywords)
- Cell cycle
- Intracellular compartmentalisation
- Protein sorting
- trafficking
- targeting
- Secretion
- Vesicle trafficking