Myosin V functions as an actin-dependent ATPase. In Drosophila it is enriched in the brain. Identification of a mutant bearing a P-lacW insertion 600 bp from the ATG initiation site in the myosin V gene of Drosophila melanogaster has enabled us to study the effects of limited myosin V on the developing fly. Maternally contributed mRNA may support the survival of the homozygote mutant larva into the later larval stages since there are no apparent behavioral or developmental defects in either embryos or in early instar larvae. Neurological problems are first evident in the 3rd instar, where the distal portion of the larva is paralyzed which decreases the force and propagation of the peristaltic wave which propels them forward. These neurological defects are magnified in the adult stages in which mutants are slow moving and unable to jump or fly. They also exhibit a general tremor of their head and legs. This chorea progresses rapidly, with newly hatched flies tending to move around at an almost normal rate, with movement becoming slower and less coordinated until death at 1 week. The homozygous P-element inserted flies are either severe hypomorphs or functional nulls for myosin V as no protein could be detected by Western blotting with a myosin V antibody from quantities of fly heads that yield an easily detectable signal in wild type and heterozyogotes. We plan to use these flies as the background for transgenic rescue experiments with myosin V constructs. In addition, we have cloned a novel myosin VII isoform from Drosophila and will be studying its properties.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Intramural Research (Z01)
Project #
1Z01HL004227-06
Application #
6432707
Study Section
(LMC)
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2000
Total Cost
Indirect Cost
Name
U.S. National Heart Lung and Blood Inst
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Mermall, Valerie; Bonafe, Nathalie; Jones, Lynn et al. (2005) Drosophila myosin V is required for larval development and spermatid individualization. Dev Biol 286:238-55
Toth, Judit; Kovacs, Mihaly; Wang, Fei et al. (2005) Myosin V from Drosophila reveals diversity of motor mechanisms within the myosin V family. J Biol Chem 280:30594-603