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Mol. Cell. Biol., 05 1996, 1966-1977, Vol 16, No. 5
T Dick, K Ray, HK Salz and W Chia
We report the molecular and genetic characterization of the cytoplasmic
dynein light-chain gene, ddlc1, from Drosophila melanogaster. ddlc1 encodes
the first cytoplasmic dynein light chain identified, and its genetic
analysis represents the first in vivo characterization of cytoplasmic
dynein function in higher eucaryotes. The ddlc1 gene maps to 4E1-2 and
encodes an 89-amino-acid polypeptide with a high similarity to the axonemal
8-kDa outer-arm dynein light chain from Chlamydomonas flagella.
Developmental Northern (RNA) blot analysis and ovary and embryo RNA in situ
hybridizations indicate that the ddlc1 gene is expressed ubiquitously.
Anti-DDLC1 antibody analyses show that the DDLC1 protein is localized in
the cytoplasm. P-element-induced partial-loss-of-function mutations cause
pleiotropic morphogenetic defects in bristle and wing development, as well
as in oogenesis, and hence result in female sterility. The morphological
abnormalities found in the ovaries are always associated with a loss of
cellular shape and structure, as visualized by a disorganization of the
actin cytoskeleton. Total-loss-of-function mutations cause lethality. A
large proportion of mutant animals degenerate during embryogenesis, and the
dying cells show morphological changes characteristic of apoptosis, namely,
cell and nuclear condensation and fragmentation, as well as DNA
degradation. Cloning of the human homolog of the ddlc1 gene, hdlc1,
demonstrates that the dynein light-chain 1 is highly conserved in flies and
humans. Northern blot analysis and epitope tagging show that the hdlc1 gene
is ubiquitously expressed and that the human dynein light chain 1 is
localized in the cytoplasm. hdlc1 maps to 14q24.
Copyright © 1996, American Society for Microbiology
Cytoplasmic dynein (ddlc1) mutations cause morphogenetic defects and apoptotic cell death in Drosophila melanogaster
Institute of Molecular and Cell Biology, National University of Singapore.
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