C. elegans apoptosis : CED-4 translocation and involvement in a model of mucolipidosis type IV human lysosomal storage disorder
Name
50444830-MIT.pdf
Description
Full printable version
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12.86 MB
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Checksum (MD5)
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Author(s)
Hersh, Bradley Michael, 1973-
Advisor(s)
H. Robert Horvitz.
Alternative Title
Caenorhabditis elegans apoptosis
Date Issued
2002
Publisher
Massachusetts Institute of Technology
Abstract
The process of programmed cell death is important in the development and homeostasis of multicellular organisms. The conserved morphological events of this process have been termed apoptosis. The molecular mechanisms of apoptosis execution are also conserved. We have investigated the behavior of these shared components during programmed cell death in the nematode Caenorhabditis elegans. We have found that the CED-9 protein, an anti-apoptotic member of the Bcl-2 family of apoptotic regulators, is required for the sequestering of the CED-4 cell-death activator to mitochondria. In the absence of CED-9 in C. elegans embryos, we found that CED-4 protein translocates to the nuclear membrane. In addition, inducing excess programmed cell death by expression of the EGL-1 cell-death activator triggers the translocation of CED-4 from mitochondria to the nuclear membrane. We performed a genetic screen for mutations that trigger programmed cell death in ced-9 gain-of-function animals where cell death is blocked. We identified a mutation in cup-5, the C. elegans homolog of the human mucolipidosis type IV gene, which is mutated in a lysosomal storage disorder. We found that cup-5 is required for viability and that excess lysosomes accumulate in cup-5 mutants. In addition, cup--5 mutants contain excess programmed cell deaths, suggesting that apoptosis may play a role in the pathology of mucolipidosis type IV.
Description
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, February 2002.
Includes bibliographical references.
Subjects
Biology.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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