| Autor: |
Inoue E; KAN Research Institute, Kyoto 600-8815, Japan., Deguchi-Tawarada M, Takao-Rikitsu E, Inoue M, Kitajima I, Ohtsuka T, Takai Y |
| Jazyk: |
angličtina |
| Zdroj: |
Genes to cells : devoted to molecular & cellular mechanisms [Genes Cells] 2006 Jun; Vol. 11 (6), pp. 659-72. |
| DOI: |
10.1111/j.1365-2443.2006.00970.x |
| Abstrakt: |
The active zone protein CAST binds directly to the other active zone proteins RIM, Bassoon and Piccolo, and it has been suggested that these protein-protein interactions play an important role in neurotransmitter release. To further elucidate the molecular mechanism, we attempted to examine the function of CAST using PC12 cells as a model system. Although PC12 cells do not express CAST, they do express ELKS, a protein structurally related to CAST. Endogenous and exogenously expressed ELKS, RIM2 and Bassoon were colocalized in punctate signals in PC12 cells. Over-expression of full-length ELKS resulted in a significant increase in stimulated exocytosis of human growth hormone (hGH) from PC12 cells, similar to the effect of full-length RIM2. This increase was not observed following over-expression of deletion constructs of ELKS that lacked either the last three amino acids (IWA) required for binding to RIM2 or a central region necessary for binding to Bassoon. Moreover, over-expression of the NH(2)-terminal RIM2-binding domain of Munc13-1, which is known to inhibit the binding between RIM and Munc13-1, inhibited the stimulated increase in hGH secretion by full-length RIM2. Furthermore, this construct also inhibited the stimulated increase in hGH secretion induced by full-length ELKS. These results suggest that ELKS is involved in Ca(2+)-dependent exocytosis from PC12 cells at least partly via the RIM2-Munc13-1 pathway. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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