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dictyNews Volume 34 Number 18
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.
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Abstracts
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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]
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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]
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[End dictyNews, volume 34, number 18]
