コレステロール輸送型のヘッジホッグ受容体の構造的基礎
Yunxiao Zhang1, David P Bulkley2, Yao Xin3
1Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94158, USA.
Cell
|November 13, 2018
まとめ
パッチされた (PTCH1) タンパク質は,コレステロールの可用性を制御し,ヘッジホッグのシグナル伝達と基礎細胞癌の発達に影響を与える. これは,コレステロール輸送における PTCH1 の新しい役割を示唆しています.
科学分野:
- 分子生物学
- セル・シグナル
- 構造生物学
背景:
- ヘッジホッグ (Hh) タンパク質は組織の発達と維持に不可欠です.
- パッチド (PTCH1) は,Hh経路の重要な構成要素であるスムージド (SMO) を阻害する12トランスメブラン受容体である.
- PTCH1機能の喪失は基礎細胞癌 (BCC) と関連しています.
研究 の 目的:
- PTCH1機能の構造的基礎を明らかにする.
- PTCH1,SMO,およびコレステロールの関係を調査する.
- Hh経路の調節における PTCH1の役割を理解する.
主な方法:
- PTCH1の構造を決定するための冷凍電子顕微鏡 (冷凍EM)
- RNDトランスポーターとのトランスメブラン領域類似性の分析.
- PTCH1とHh刺激に対するコレステロールの活性に関する調査.
主要な成果:
- PTCH1は,水害性管を特徴とする,プロカリオットRNDトランスポーターと構造的類似性を共有しています.
- この管にはコレステロールのような分子が含まれており,コレステロールの輸送に役割があることを示唆しています.
- PTCH1の発現は,Hhシグナル伝達によって回復される血のコレステロールを減少させる.
結論:
- PTCH1はコレステロールトランスポーターとして機能する.
- PTCH1は,血膜におけるコレステロールの可用性を調節することによって,SMOの活性を調節する.
- このメカニズムは,Hh経路の調節とBCCの病原性に関する新しい洞察を提供します.
関連する概念動画
01:55Secondary Active Transport
137.9K
One example of how cells use the energy contained in electrochemical gradients is demonstrated by glucose transport into cells. The ion vital to this process is sodium (Na+), which is typically present in higher concentrations extracellularly than in the cytosol. Such a concentration difference is due, in part, to the action of an enzyme “pump” embedded in the cellular membrane that actively expels Na+ from a cell. Importantly, as this pump contributes to the high concentration of...
137.9K
01:32Secondary Active Transport
9.6K
One example of how cells use the energy contained in electrochemical gradients is demonstrated by glucose transport into cells. The ion vital to this process is sodium (Na+), which is typically present in higher concentrations extracellularly than in the cytosol. Such a concentration difference is due, in part, to the action of an enzyme "pump" embedded in the cellular membrane that actively expels Na+ from a cell. Importantly, as this pump contributes to the high concentration of...
9.6K
01:47Primary Active Transport
198.5K
In contrast to passive transport, active transport involves a substance being moved through membranes in a direction against its concentration or electrochemical gradient. There are two types of active transport: primary active transport and secondary active transport. Primary active transport utilizes chemical energy from ATP to drive protein pumps that are embedded in the cell membrane. With energy from ATP, the pumps transport ions against their electrochemical gradients—a direction...
198.5K
01:29Primary Active Transport
14.2K
In contrast to passive transport, active transport involves a substance being moved through membranes in a direction against its concentration or electrochemical gradient. There are two types of active transport: primary active transport and secondary active transport. Primary active transport utilizes chemical energy from ATP to drive protein pumps embedded in the cell membrane. With energy from ATP, the pumps transport ions against their electrochemical gradients—a direction they would...
14.2K
01:14Active Transport
2.1K
Active transport is a critical biological process that allows cells to move solutes against an electrochemical gradient. This process requires direct energy input and is characterized by its selectivity, saturability, and susceptibility to competitive inhibition.
Primary active transporters, like Na+, K+ and -ATPase, directly utilize ATP to move ions across the membrane. These transporters play significant roles in various physiological processes. For instance, Na+, K+ and -ATPase maintain...
Primary active transporters, like Na+, K+ and -ATPase, directly utilize ATP to move ions across the membrane. These transporters play significant roles in various physiological processes. For instance, Na+, K+ and -ATPase maintain...
2.1K
01:39Receptor-mediated Endocytosis
110.9K
Overview
110.9K