dictyNews
Electronic Edition
Volume 34, number 18
June 11, 2010

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=========
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 [[log in to unmask]]
--------------------------------------------------------------------------------


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 [[log in to unmask]]
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[End dictyNews, volume 34, number 18]