dictyNews Electronic Edition Volume 34, number 18 June 11, 2010 Please submit abstracts of your papers as soon as they have been accepted for publication by sending them to dicty@northwestern.edu or by using the form at http://dictybase.org/db/cgi-bin/dictyBase/abstract_submit. Back issues of dictyNews, the Dicty Reference database and other useful information is available at dictyBase - http://dictybase.org. Follow dictyBase on twitter: http://twitter.com/dictybase ========= Abstracts ========= Pregnenolone sulfate and cortisol induce secretion of acyl coa binding protein and its conversion into endozepines from astrocytes William F. Loomis 1*, M. Margarita Behrens 2, Megan E. Williams 1, and Christophe Anjard1* From Division of Biological Sciences1, University of California San Diego, La Jolla, CA and The Salk Institute2, La Jolla, CA JBC, in press Acyl CoA binding protein (ACBP) functions both intracellularly as part of fatty acid metabolism and extracellularly as DBI, the precursor of endozepine peptides. Two of these peptides, ODN and TTN, bind to the GABAA receptor and modulate its sensitivity to GABA. We have found that depolarization of mouse primary astrocytes induces the rapid release and processing of ACBP to the active peptides. We previously showed that ODN can trigger the rapid sporulation of the social amoeba Dictyostelium. Using this bioassay, we now show that astrocytes release the endozepine peptides within 10 minutes of exposure to the steroids cortisol, pregnenolone, pregnenolone sulfate or progesterone. ACBP lacks a signal sequence for secretion through the ER/Golgi pathway and its secretion is not affected by addition of Brefeldin A, a well known inhibitor of the classical secretion pathway, suggesting that it follows an unconventional pathway for secretion. Moreover, induction of autophagy by addition of rapamycin also resulted in rapid release of ACBP indicating that this protein uses components of the autophagy pathway for secretion. Following secretion, ACBP is proteolytically cleaved to the active neuropeptides by protease activity on the surface of astrocytes. Neurosteroids, such as pregnenolone sulfate, were previously shown to modulate the excitatory/inhibitory balance in brain through increased release of glutamate and decreased release of GABA. These effects of steroids in neurons will be reinforced by the release of endozepines from astrocytes shown here, and suggest an orchestrated astrocyte-neuron cross talk that can affect a broad spectrum of behavioral functions. Submitted by Christophe Anjard [canjard@ucsd.edu] -------------------------------------------------------------------------------- Novel Prenylated and Geranylated Aromatic Compounds Isolated from Polysphondylium Cellular Slime Molds Haruhisa Kikuchi, Shinya Ishiko, Koji Nakamura, Yuzuru Kubohara, and Yoshiteru Oshima Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba-yama, Aoba-ku, Sendai 980-8578, Japan (HK, SI, KN, YO). Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512, Japan (YK). Tetrahedron, In press We have studied the diversity of secondary metabolites of cellular slime molds to utilize them as new biological resources for natural product chemistry. From the methanol extract of fruiting bodies of Polysphondylium tenuissimum, we obtained five prenylated and geranylated aromatic compounds, Pt-1~5 (1-5). An additional aromatic compound, Ppc-1 (6), was isolated from P. pseudo-candidum. The structures of these compounds were determined by spectral analysis, and synthetic routes to 4, 5, and 6 were developed. Compound 5 showed the glucose consumption-promotive activity on 3T3-L1 cells. Submitted by Yuzuru Kubohara [kubohara@showa.gunma-u.ac.jp] ============================================================== [End dictyNews, volume 34, number 18]