HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE ADVANCED SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Inoue, E. Articles by Takai, Y. Search for Related Content PubMed PubMed Citation Articles by Inoue, E. Articles by Takai, Y.

¹ KAN Research Institute, Kyoto 600-8815, Japan
² Department of Clinical and Molecular Pathology, Faculty of Medicine/Graduate School of Medicine, University of Toyama, Toyama 930-0194, Japan
³ CREST, Japan Science and Technology Agency, Kawaguchi 332-0012,Japan
⁴ Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita 565-0871, Japan

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 NH₂-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 Ca²⁺-dependent exocytosis from PC12 cells at least partly via the RIM2-Munc13-1 pathway.

^* Correspondence: E-mail: tohtsuka{at}med.u-toyama.ac.jp

This article has been cited by other articles:

				E. P. Kwan, L. Xie, L. Sheu, T. Ohtsuka, and H. Y. Gaisano Interaction Between Munc13-1 and RIM Is Critical for Glucagon-Like Peptide-1 Mediated Rescue of Exocytotic Defects in Munc13-1 Deficient Pancreatic {beta}-Cells Diabetes, October 1, 2007; 56(10): 2579 - 2588. [Abstract] [Full Text] [PDF]