ELKS, a protein structurally related to the active zone protein CAST, is involved in Ca2+-dependent exocytosis from PC12 cells
| Autor: | Isao Kitajima, Etsuko Takao-Rikitsu, Toshihisa Ohtsuka, Eiji Inoue, Yoshimi Takai, Marie Inoue, Maki Deguchi-Tawarada |
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| Rok vydání: | 2006 |
| Předmět: |
Molecular Sequence Data
Nerve Tissue Proteins Biology PC12 Cells Exocytosis Protein structure Genetics Animals Humans Secretion Amino Acid Sequence Active zone Binding site Cells Cultured Adaptor Proteins Signal Transducing chemistry.chemical_classification Binding Sites Sequence Homology Amino Acid Human Growth Hormone Signal transducing adaptor protein Cell Biology Protein Structure Tertiary Rats Amino acid Cell biology Biochemistry chemistry Multiprotein Complexes Calcium Signal transduction Signal Transduction |
| Zdroj: | Genes to Cells. 11:659-672 |
| ISSN: | 1365-2443 1356-9597 |
| DOI: | 10.1111/j.1365-2443.2006.00970.x |
| Popis: | 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: | OpenAIRE |
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