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Endocytic trafficking is required for neuron cell death through regulating TGF-beta signaling in <i>Drosophila melanogaster</i>

Programmed cell death (PCD) is an essential feature during the development of the central nervous system in Drosophila as well as in mammals. During metamorphosis, a group of peptidergic neurons (vCrz) are eliminated from the larval central nervous system (CNS) via PCD within 6-7 h after puparium formation. To better understand this process, we first characterized the development of the vCrz neurons including their lineages and birth windows using the MARCM (Mosaic Analysis with a Repressible Cell Marker) assay. Further genetic and MARCM analyses showed that not only Myoglianin (Myo) and its type I receptor Baboon is required for neuron cell death, but also this death signal is extensively regulated by endocytic trafficking in Drosophila melanogaster. We found that clathrin-mediated membrane receptor internalization and subsequent endocytic events involved in Rab5-dependent early endosome and Rab11-dependent recycling endosome differentially participate in TGF-β [beta] signaling. Two early endosome-enriched proteins, SARA and Hrs, are found to act as a cytosolic retention factor of Smad2, indicating that endocytosis mediates TGF-β [beta] signaling through regulating the dissociation of Smad2 and its cytosolic retention factor.

Identiferoai:union.ndltd.org:UTENN/oai:trace.tennessee.edu:utk_graddiss-2273
Date01 August 2011
CreatorsWang, Zixing
PublisherTrace: Tennessee Research and Creative Exchange
Source SetsUniversity of Tennessee Libraries
Detected LanguageEnglish
Typetext
Formatapplication/pdf
SourceDoctoral Dissertations

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