EMBRYONIC DORSOVENTRAL POLARITY IN DROSOPHILA
EMBRYONIC DORSOVENTRAL POLARITY IN DROSOPHILA
批准号:
2459489
负责人:
CARL HASHIMOTO
金额:
$28.75万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1992
资助国家:
美国
项目状态:
已结题
起止时间:
1992-08-01 至 1999-07-31
关键词:
Drosophilidae affinity chromatography binding proteins biological signal transduction cell membrane cellular polarity early embryonic stage electron microscopy enzyme activity enzyme substrate immunochemistry immunoprecipitation membrane proteins oogenesis polymerase chain reaction protein structure function serine proteinases western blottings
中文摘要
果蝇胚胎的背、腹侧极性是由a
英文摘要
Dorsoventral polarity of the Drosophila embryo is established by a
transmembrane signaling pathway involving maternal molecules. Two
outstanding questions about this pathway concern how the extracellular
signal that induces polarity is asymmetrically generated and how it is
transmitted to the interior of the embryo. The extracellular signal is the
ligand for the transmembrane Toll protein, which is similar in its
cytoplasmic domain to the mammalian interleukin l receptor. Activation of
either protein causes, by an unclear mechanism, the nuclear targeting of
a rel proto-oncogene transcription factor. Earlier studies suggested that
localized activation of a protease cascade restricts production of Toll's
ligand to the ventral side of the embryo, and that this localized
activation is determined by a component asymmetrically laid down during
oogenesis in the future extracellular compartment of the embryo. We
recently uncovered a possible clue to how Toll's ligand is asymmetrically
produced. We cloned and sequenced the nudel gene, which is expressed
during oogenesis and is required to activate the proteases that produce
Toll's ligand. The nudel gene product is predicted to be a large (greater
than or equal to 300 kD) extracellular glycoprotein, modular like
extracellular matrix molecules, with cysteine-rich motifs first seen in
the mammalian LDL receptor. Nudel's most intriguing structural motif is a
serine protease domain, so it may initiate the protease cascade producing
Toll's ligand. Since the nuclei RNA appears to be ventrally enriched in
the egg chamber during oogenesis, the nudel protein may also function as
a spatial determinant of embryonic dorsoventral polarity.
Our long-term goal is to understand in biochemical detail how the nudel
protein activates and localizes the proteases that produce Toll's ligand,
and how Toll activates intracellular signaling reactions. Specific aims
are: l) Immunolocalize the nudel protein in egg chambers and embryos to
determine if it is ventrally enriched; and perform fractionation
experiments to determine if nudel is bound to the embryonic plasma
membrane or the surrounding vitelline envelope, since it must be non-
diffusible in order to localize protease activation. 2) Test nudel's
serine protease and other functions in embryos using a combination of in
vitro mutagenesis, germline transformation, and RNA injection methods. 3)
Identify nudel's protease substrate and other molecules that bind to nudel
using in vitro protease assays, immunoprecipitation methods, and affinity
chromatography. 4) Identify proteins that bind to Toll's cytoplasmic
domain through immunoisolation, affinity chromatography, and the yeast
interaction trap screen. The proposed studies on nudel and Toll, and their
interacting proteins, will increase our understanding of similar molecules
involved in cancer and cardiovascular disorders.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Yale Postbaccalaureate Research Education Program
-
批准号:8636742
-
项目类别:
-
资助金额:$26.18万
-
财政年份:2014
-
负责人:CARL HASHIMOTO
-
依托单位:
Biology of Serine Proteases and Serpins
-
批准号:8008953
-
项目类别:
-
资助金额:$11.15万
-
财政年份:2010
-
负责人:CARL HASHIMOTO
-
依托单位:
EMBRYONIC DORSOVENTRAL POLARITY IN DROSOPHILA
-
批准号:6128908
-
项目类别:
-
资助金额:$32.67万
-
财政年份:1992
-
负责人:CARL HASHIMOTO
-
依托单位:
EMBRYONIC DORSOVENTRAL POLARITY IN DROSOPHILA
-
批准号:6546804
-
项目类别:
-
资助金额:$2.49万
-
财政年份:1992
-
负责人:CARL HASHIMOTO
-
依托单位:
ROLE OF THE TOLL PROTEIN IN EMBRYOGENESIS
-
批准号:3308728
-
项目类别:
-
资助金额:$0.18万
-
财政年份:1992
-
负责人:CARL HASHIMOTO
-
依托单位:
Biology of Serine Proteases and Serpins
-
批准号:7324774
-
项目类别:
-
资助金额:$34.88万
-
财政年份:1992
-
负责人:CARL HASHIMOTO
-
依托单位:
Biology of Serine Proteases and Serpins
-
批准号:7151915
-
项目类别:
-
资助金额:$34.88万
-
财政年份:1992
-
负责人:CARL HASHIMOTO
-
依托单位:
Biology of Serine Proteases and Serpins
-
批准号:6869656
-
项目类别:
-
资助金额:$35.27万
-
财政年份:1992
-
负责人:CARL HASHIMOTO
-
依托单位:
EMBRYONIC DORSOVENTRAL POLARITY IN DROSOPHILA
-
批准号:6385816
-
项目类别:
-
资助金额:$32.67万
-
财政年份:1992
-
负责人:CARL HASHIMOTO
-
依托单位:
EMBRYONIC DORSOVENTRAL POLARITY IN DROSOPHILA
-
批准号:6636084
-
项目类别:
-
资助金额:$32.67万
-
财政年份:1992
-
负责人:CARL HASHIMOTO
-
依托单位:
TOLL PROTEIN AND EMBRYOGENESIS
-
批准号:2186965
-
项目类别:
-
资助金额:$17.55万
-
财政年份:1992
-
负责人:CARL HASHIMOTO
-
依托单位:
EMBRYONIC DORSOVENTRAL POLARITY IN DROSOPHILA
-
批准号:2749939
-
项目类别:
-
资助金额:$30.41万
-
财政年份:1992
-
负责人:CARL HASHIMOTO
-
依托单位:
EMBRYONIC DORSOVENTRAL POLARITY IN DROSOPHILA
-
批准号:6519540
-
项目类别:
-
资助金额:$35.16万
-
财政年份:1992
-
负责人:CARL HASHIMOTO
-
依托单位:
ROLE OF THE TOLL PROTEIN IN EMBRYOGENESIS
-
批准号:3308727
-
项目类别:
-
资助金额:$16.05万
-
财政年份:1992
-
负责人:CARL HASHIMOTO
-
依托单位:
ROLE OF THE TOLL PROTEIN IN EMBRYOGENESIS
-
批准号:3308729
-
项目类别:
-
资助金额:$17.06万
-
财政年份:1992
-
负责人:CARL HASHIMOTO
-
依托单位:
EMBRYONIC DORSOVENTRAL POLARITY IN DROSOPHILA
-
批准号:2186966
-
项目类别:
-
资助金额:$23.63万
-
财政年份:1992
-
负责人:CARL HASHIMOTO
-
依托单位:
EMBRYONIC DORSOVENTRAL POLARITY IN DROSOPHILA
-
批准号:2186967
-
项目类别:
-
资助金额:$25.23万
-
财政年份:1992
-
负责人:CARL HASHIMOTO
-
依托单位:
Biology of Serine Proteases and Serpins
-
批准号:6994478
-
项目类别:
-
资助金额:$35.92万
-
财政年份:1992
-
负责人:CARL HASHIMOTO
-
依托单位:
海外基金