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Originally published In Press as doi:10.1074/jbc.M109826200 on December 13, 2001
J. Biol. Chem., Vol. 277, Issue 8, 6696-6702, February 22, 2002
Overexpression of Poly(ADP-ribose) Polymerase Disrupts
Organization of Cytoskeletal F-actin and Tissue Polarity in
Drosophila*
Masahiro
Uchida ,
Shuji
Hanai ,
Naoya
Uematsu ,
Kazunobu
Sawamoto§¶ ,
Hideyuki
Okano§¶,
Masanao
Miwa , and
Kazuhiko
Uchida **
From the Department of Biochemistry and Molecular
Oncology, Institute of Basic Medical Sciences, University of
Tsukuba, Tsukuba, Ibaraki 305-8575, Japan, the § Division of
Neuroanatomy, Department of Neuroscience, Biomedical Research Center,
Osaka University Graduate School of Medicine, Osaka 565-0871, Japan, the ¶ Core Research for Evolutional Science and
Technology (CREST), Japan Science and Technology Corporation (JST), and
the Strategic Promotion System for Brain Science (SPSBS),
Science and Technology Agency of Japan
Poly(ADP-ribose) polymerase (PARP)
may play important roles in nuclear events such as cell cycle, cell
proliferation, and maintenance of chromosomal stability. However, the
exact biological role played by PARP or how PARP is involved in these
cellular functions is still unclear. To elucidate the biological
functions of PARP in vivo, we have constructed transgenic
flies that overexpress Drosophila PARP in the developing
eye primordia. These flies showed mild roughening of the normally
smooth ommatidial lattice and tissue polarity disruption caused by
improper rotation and chirality of the ommatidia. To clarify how this
phenotypical change was induced, here we analyzed transgenic flies
overexpressing PARP in the developing eye, embryo, and adult in detail.
PARP mRNA level and the phenotype were enhanced in flies carrying
more copies of the transgene. Developing eyes from third instar larvae
were analyzed by using the neural cell marker to examine the
involvement of PARP in cell fate. Morphological disorder of
non-neuronal accessory cells was observed in PARP transgenic flies.
Interestingly, overexpression of PARP did not interfere with the cell
cycle or apoptosis, but it did disrupt the organization of cytoskeletal
F-actin, resulting in aberrant cell and tissue morphology. Furthermore,
heat-induced PARP expression disrupted organization of cytoskeletal
F-actin in embryos and tissue polarity in adult flies. Because these
phenotypes closely resembled mutants or transgenic flies of the tissue
polarity genes, genetic interaction of PARP with known tissue polarity genes was examined. Transgenic flies expressing either PARP or RhoA
GTPase in the eye were crossed, and co-expression of PARP suppressed
the effect of RhoA GTPase. Our results indicate that PARP may play a
role in cytoskeletal or cytoplasmic events in developmental processes
of Drosophila.
*
This work was supported in a part by grants-in-aid for
scientific research and cancer research from the Ministry of Education, Science, Sports and Culture, for cancer research from the Sagawa Foundation, and for a comprehensive 10-year strategy for cancer control
from the Ministry of Health and Welfare of Japan.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
**
To whom correspondence should be addressed: Dept. of
Biochemistry and Molecular Oncology, Institute of Basic Medical
Science, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki
305-8575, Japan. Tel.: 81-298-53-3272; Fax: 81-298-53-3271; E-mail:
kzuchida@md.tsukuba.ac.jp.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.

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