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J Physiol Volume 538, Number 1, 103-119, January 1, 2002 DOI: 10.1113/jphysiol.2001.012901
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Journal of Physiology (2002), 538.1, pp. 103-119
© Copyright 2002 The Physiological Society
DOI: 10.1113/jphysiol.2001.012901

Hypertonicity-induced transmitter release at Drosophila neuromuscular junctions is partly mediated by integrins and cAMP/protein kinase A

Kazuhiro Suzuki, Alan D. Grinnell* and Yoshiaki Kidokoro

Institute for Behavioral Sciences, Gunma University School of Medicine, 3-39-22 Showa-machi, Maebashi, 371-8511, Japan and *Jerry Lewis Neuromuscular Research Center, UCLA School of Medicine, Los Angeles, CA 90024, USA

The frequency of quantal transmitter release increases upon application of hypertonic solutions. This effect bypasses the Ca2+ triggering step, but requires the presence of key molecules involved in vesicle fusion, and hence could be a useful tool for dissecting the molecular process of vesicle fusion. We have examined the hypertonicity response at neuromuscular junctions of Drosophila embryos in Ca2+-free saline. Relative to wild-type, the response induced by puff application of hypertonic solution was enhanced in a mutant, dunce, in which the cAMP level is elevated, or in wild-type embryos treated with forskolin, an activator of adenylyl cyclase, while protein kinase A (PKA) inhibitors decreased it. The response was also smaller in a mutant, DC0, which lacks the major subunit of PKA. Thus the cAMP/PKA cascade is involved in the hypertonicity response. Peptides containing the sequence Arg-Gly-Asp (RGD), which inhibit binding of integrins to natural ligands, reduced the response, whereas a peptide containing the non-binding sequence Arg-Gly-Glu (RGE) did not. A reduced response persisted in a mutant, myospheroid, which expresses no integrins, and the response in DC0 was unaffected by RGD peptides. These data indicate that there are at lease two components in the hypertonicity response: one that is integrin mediated and involves the cAMP/PKA cascade, and another that is not integrin mediated and does not involve the cAMP/PKA cascade.



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