Copy Link
Add to Bookmark
Report
dictyNews Volume 39 Number 07
dictyNews
Electronic Edition
Volume 39, number 7
March 8, 2013
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
=========
Antagonistic control of lysosomal fusion by Rab14 and the Lyst-related
protein LvsB.
Elena Kypri, Kristin Falkenstein, and Arturo De Lozanne
Section of Molecular Cell & Developmental Biology and Institute for Cellular
and Molecular Biology, University of Texas at Austin, Austin, TX 78712.
Traffic, in press
While loss of the protein Lyst causes abnormal lysosomes in patients with
Chediak-Higashi Syndrome, the contribution of Lyst to lysosome biology is
not known. Previously we found that the Dictyostelium ortholog of Lyst, LvsB,
is a cytosolic protein that associates with lysosomes and post-lysosomes to
prevent their inappropriate fusion. Here we provide three lines of evidence
that indicate that LvsB contributes to lysosome function by antagonizing the
function of DdRab14, a protein that promotes homotypic fusion among
lysosomes. (1) Instead of restricting DdRab14 to lysosomes, cells that lack
LvsB expand DdRab14 localization to include post-lysosomes. (2)
Expression of activated DdRab14 phenocopies the loss of LvsB, causing
inappropriate heterotypic fusion between lysosomes and post-lysosomes
and their subsequent enlargement. (3) Conversely, expression of inactivated
DdRab14 suppresses the phenotype of LvsB null cells and restores their
lysosomal size and segregation from post-lysosomes. Our data suggest a
scenario where LvsB binds to late lysosomes and promotes the inactivation
of DdRab14. This inactivation allows the lysosomes to mature into post-
lysosomes for eventual secretion. We propose that human Lyst may function
similarly to regulate Rab-dependent fusion of lysosomal compartments.
Submitted by Arturo De Lozanne [a.delozanne@utexas.edu]
---------------------------------------------------------------------------
Derivatives of Dictyostelium discoideum differentiation-inducing factor-3
suppress the activities of Trypanosoma cruzi in vitro and in vivo
Junko Nakajima-Shimada 1*, Toshimitsu Hatabu a, Yukari Hosoi 1, Yoko
Onizuka 1, Haruhisa Kikuchi 2, Yoshiteru Oshima 2, Yuzuru Kubohara 3*
1 Graduate School of Health Sciences, Gunma University, Maebashi
371-8514, Japan
2 Graduate School of Pharmaceutical Sciences, Tohoku University,
Sendai 980-8578, Japan
3 Institute for Molecular and Cellular Regulation (IMCR), Gunma University,
Maebashi 371-8512, Japan
Biochemical Pharmacology, in press
Chagas disease (human American trypanosomiasis), which is caused by
the protozoan parasite Trypanosoma cruzi, is responsible for numerous
deaths each year; however, established treatments for the disease are
limited. Differentiation-inducing factor-1 (DIF-1) and DIF-3 are chlorinated
alkylphenones originally found in the cellular slime mold Dictyostelium
discoideum that have been shown to possess pharmacological activities.
Here, we investigated the effects of DIF-3 derivatives on the infection rate
and growth of T. cruzi by using an in vitro assay system utilizing host human
fibrosarcoma HT1080 cells. Certain DIF-3 derivatives, such as butoxy-DIF-3
(Bu-DIF-3), at micro-molar levels strongly suppressed both the infection rate
and growth of T. cruzi in HT1080 cells and exhibited little toxicity for HT1080
cells. For example, the IC50 of DIF-3 and Bu-DIF-3 versus the growth of
T. cruzi in HT1080 cells were 3.95 and 0.72 uM, respectively, and the LD50
of the two compounds versus HT1080 cells were both greater than 100 uM.
We also examined the effects of DIF-3 and Bu-DIF-3 on T. cruzi activity in
C57BL/6 mice. Intraperitoneally administered Bu-DIF-3 (50 mg/kg)
significantly suppressed the number of trypomastigotes in blood with no
apparent adverse effects. These results strongly suggest that DIF-3
derivatives could be new lead compounds in the development of anti-
trypanosomiasis drugs.
Submitted by Yuzuru Kubohara [kubohara@showa.gunma-u.ac.jp]
==============================================================
[End dictyNews, volume 39, number 7]
