Dishevelledによる致命的な巨大幼虫の規制
Gretchen L Dollar1, Ursula Weber, Marek Mlodzik
1Department of Molecular, Cell and Developmental Biology, Box 1020, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, New York 10029, USA.
Nature
|October 28, 2005
まとめ
致死性巨大幼虫 (Lgl) のタンパク質の局所化と活動は,細胞の極性にとって不可欠であり,Dishevelled (Dsh) とWntシグナリングによって調節されます. これは,発達中の細胞の極化を制御する分子機構を明らかにしています.
科学分野:
- 細胞生物学 細胞生物学
- 発達生物学 発達生物学とは
- 分子シグナル伝達です.
背景:
- 細胞の極性は,組織の発達と機能に不可欠である.
- 致死性巨大幼虫 (Lgl) タンパク質は,細胞の極性および基礎側タンパク質標的化の主要な調節剤です.
- 細胞の偏極化を制御する正確なシグナル伝達経路は,まだ完全に理解されていません.
研究 の 目的:
- Lglの局所化と細胞の極性調節におけるDishevelled (Dsh) の役割を調査する.
- Lglの活性制御におけるWnt信号伝達経路の関与を明らかにする.
- 細胞の極性に対するWnt媒介による調節の基礎となる分子メカニズムを定義する.
主な方法:
- LglとDishevelled (Dsh) の関連性をXenopus ectodermとDrosophilaの葉っぱ表皮で調査した.
- XenopusとDrosophilaのモデルを使用して,LglとDshの機能的要件を研究し,頂点-基礎の極性を確立しました.
- Wnt受容体Frizzled 8の活性化がLglの局所化と活性化に及ぼす効果を研究した.
主要な成果:
- 脊椎動物のLglホモログがDishevelled (Dsh) と関連していることを実証しました.
- Dshは,Xenopus ectodermとDrosophilaの葉っぱの表皮の両方でLglの局所化を調節することを示しました.
- LglとDshの両方が,Xenopusの外皮細胞の正常なアピカル・ベース・ポラリティに不可欠であることを確認しました.
- Frizzled 8の活性化が,Frizzled 7の活性化ではないが,Lglが皮質から解離され,その活動が失われることを発見した.
結論:
- Dishevelled (Dsh) は,Lethal giant larva (Lgl) タンパク質の局所化と活性を調節する上で重要な役割を果たしています.
- Wntシグナル伝達,特にFrizzled 8を通じて,Lglの機能に直接影響を及ぼし,Wnt経路と細胞の極性との間の分子リンクを提供します.
- これらの発見は,FrizzledとDishevelledが発達中の細胞の極性をどのように調整するかを理解するための新しい分子枠組みを提供します.
関連する概念動画
02:41Lethal Alleles
Agouti: A Lethal Allele
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
02:45The Ratio of X Chromosome to Autosomes
In most organisms, sex is determined by the ratio of X and Y chromosomes. However, in some organisms, such as Drosophila and C.elegans, sex is determined by the ratio of the number of X chromosomes to the number of sets of autosomes. The Y chromosome in Drosophila is active but does not determine sex. It contains genes responsible for the production of sperms in adult flies.
Normal male Drosophila has a ratio of one X chromosome to two sets of autosomes. In contrast, normal female Drosophila...
Normal male Drosophila has a ratio of one X chromosome to two sets of autosomes. In contrast, normal female Drosophila...
02:50Dosage Compensation
In animals, gender is determined by the number and type of sex chromosome. For example, human females have two X chromosomes, and males have one X and one Y chromosome, whereas C.elegans with one X chromosome is a male, and the one with two X chromosomes is a hermaphrodite.
In addition to sexual development, the X chromosome has genes involved in autosomal functions such as brain development and the immune system. Therefore, males and females with distinct numbers of X chromosomes will have...
In addition to sexual development, the X chromosome has genes involved in autosomal functions such as brain development and the immune system. Therefore, males and females with distinct numbers of X chromosomes will have...
02:33Hedgehog Signaling Pathway
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...