Name: how integrins link cells to their environment
Uploaded: 2023-04-30T11:54:20.000Z
Duration: 1 min 15 s
Channel: JoVE

세포가 ECM을 통해 이동하려면 ECM에 대한 세포의 부착이 신속하게 이루어지고 끊어져야 합니다.
이것은 부착물을 형성하는 활성 상태와 그렇지 않은 비활성 상태 사이에서 빠르게 전환되는 막 결합 인테그린에 의해 촉진됩니다.
비활성 형태에서는 인테그린 이량체의 꼬리가 조밀하게 고정되어 인테그린이 ECM 단백질 또는 세포골격 필라멘트에 결합하는 것을 방지합니다.
인테그린은 "외부-내부" 메커니즘 또는 "내부-외부" 메커니즘에서 세포 외부에서 활성화될 수 있습니다.
"아웃사이드-인(outside-in)" 메커니즘에서 피브로넥틴(fibronectin)과 같은 ECM 단백질은 인테그린의 세포외 도메인(extracellular domain)에 결합합니다. 꼬리가 풀리고 인테그린이 비활성 상태에서 활성 상태로 전환되어 세포질 어댑터 단백질의 결합 부위가 노출됩니다.
반대로, "인사이드-아웃" 메커니즘에서 탈린과 같은 어댑터 단백질은 인테그린의 세포질 베타 사슬에 결합하여 알파-베타 연결을 끊고 인테그린 다리를 강제로 분리합니다. 활성 인테그린은 이제 ECM 단백질에 결합할 수 있습니다.

<ol>
	<li>Ginsberg, M. H., Partridge, A. 및 Shattil, S. J. (2005). 인테그린 조절. 세포 생물학의 현재 의견, 17(5), 509-516.</li>
	<li>David G. Menter, Raymond N. DuBois, "Prostaglandins in Cancer Cell Adhesion, Migration, and Invasion," International Journal of Cell Biology, vol. 2012, Article ID 723419, 21 pages, 2012. <a href="https://doi.org/10.1155/2012/723419">https://doi.org/10.1155/2012/723419</a></li>
	<li>캠벨, I. D., & 험프리스, M. J. (2011). 인테그린 구조, 활성화 및 상호 작용. 생물학의 콜드 스프링 하버 관점, 3(3), a004994.</li>
</ol>

인테그린의 활성화

Activation of Integrins

인테그린은 리간드와 결합하고 "외부 내부 신호 전달" 또는 "내부 외부 신호 전달"을 통해 세포 외부에서 내부로 또는 그 반대로 정보를 전달합니다.

"아웃사이드-인 신호전달"에서, 세포외 공간의 외부 요인은 인테그린의 노출된 리간드 결합 부위에 결합합니다. 이로 인해 비활성 단백질이 형태 변화를 거쳐 활성 상태가 됩니다. 인테그린은 종종 세포막에 클러스터되어 있습니다. 반복적이고 규칙적인 간격의 리간드 결합 이벤트는 효과적인 자극을 제공합니다. 세포가 다양한 세포외 신호를 만나면 활성화된 인테그린은 세포 극성, 세포골격 구조, 부착, 이동, 침입, 유전자 발현, 세포 생존 및 증식과 같은 세포 특성에 영향을 미칩니다.

"인사이드-아웃 신호전달"은 탈린 또는 킨들린과 같은 세포골격 어댑터 단백질과 같은 세포내 활성제에 의존합니다. 탈린에는 β 인테그린 세포질 도메인에 대한 결합 부위, 고도로 보존된 C 말단 액틴 결합 부위 및 빈쿨린 결합 부위가 포함되어 있습니다. 킨들린은 F3 도메인, 막 결합 도메인, 인테그린, 액틴 어댑터 단백질 또는 인테그린 연결 키나제(ILK)와 상호작용하는 C 말단에 β 인테그린 세포질 꼬리 결합 부위를 포함합니다. 킨들린은 β 인테그린 세포질 도메인과 상호작용하여 인테그린 복합체의 활성화 상태를 안정화합니다. "인사이드 아웃 신호"는 세포 이동, 침입, ECM 조립 및 리모델링에 필요한 힘을 전달하는 세포외 리간드와의 인테그린 매개 접착을 강화할 수 있습니다.

AP용 Openstax Biology의 섹션 9.1 신호 분자 및 세포 수용체에서 발췌

인테그린은 리간드를 결합하고 "아웃사이드-인 신호"를 통해 세포 외부에서 내부로 또는 그 반대로 정보를 전송하거나 ...

Education

교육

JoVE Core

Cell Biology

세포생물학

Unit 1

제1단원

Cell-Matrix Interactions

세포-기질 상호작용

KEY TERMS AND CONCEPTS

주요 용어 및 개념

how integrins link cells to their environment

Integrins help cells connect with their environment and send signals across the cell membrane. They can carry information from outside the cell to the inside, or from inside the cell to the outside. These two paths are called outside-in signaling and inside-out signaling.

In outside-in signaling, molecules in the extracellular space bind to exposed ligand-binding sites on integrins. A ligand is a molecule that binds to a protein. This binding makes the inactive integrin change shape and become active. Integrins are often grouped in clusters on the cell membrane, and repeated ligand binding can create a strong signal.

Once integrins are activated, they can affect many cell features. These include cell polarity, cytoskeletal structure, adhesion, migration, invasion, gene expression, cell survival, and proliferation. This is why integrin signaling matters for how cells respond to their surroundings.

Inside-out signaling depends on internal activators such as the cytoskeletal adaptor proteins talin and kindlin. Talin has binding sites for the beta integrin cytosolic domains, a conserved C-terminal actin-binding site, and a vinculin-binding site. Kindlin has beta integrin cytosolic tail binding sites in its F3 domains, membrane-binding domains, and a C-terminus that can interact with integrins, actin adaptor proteins, or integrin-linked kinase (ILK).

Kindlin also binds the beta integrin cytoplasmic domain and helps keep the integrin complex in its activated state. Inside-out signaling can strengthen integrin-mediated adhesion to extracellular ligands. That stronger attachment helps provide the force needed for cell migration, invasion, ECM assembly, and remodeling.

How Integrins Link Cells to Their Environment

how-integrins-link-cells-to-their-environment

overview of cell-matrix interactions

ECM Proteins and Cell Signaling

The extracellular matrix, or ECM, is the material that helps hold cells together in a tissue. It also lets cells in that tissue communicate with one another. The ECM contains proteins such as fibronectin, collagen, and laminin. Collagen is the most abundant protein in this space. Collagen fibers are woven together with proteoglycans, which are protein molecules with carbohydrates attached. This mix gives the ECM its structure. It also supports cell migration and provides a scaffold for cell...

integrins

Integrins in Cell Adhesion

Integrins help animal and protozoan cells attach to the extracellular matrix, or ECM. These cells do not have cell walls, so the ECM helps maintain shape and provide structural stability. The ECM is a sticky network of carbohydrates and proteins found between adjacent cells. Some ECM proteins form a basement membrane, and other ECM parts adhere to it. Proteoglycans make up much of the ECM, while fibrous proteins such as collagen give it strength. Fibronectin connects proteoglycans and collagen...

activation of integrins

Integrins help cells connect with their environment and send signals across the cell membrane. They can carry information from outside the cell to the inside, or from inside the cell to the outside. These two paths are called outside-in signaling and inside-out signaling. In outside-in signaling, molecules in the extracellular space bind to exposed ligand-binding sites on integrins. A ligand is a molecule that binds to a protein. This binding makes the inactive integrin change shape and become...

intracellular signaling affects focal adhesions

intracellular-signaling-affects-focal-adhesions

Integrins Trigger Focal Adhesion Signaling

Integrins trigger focal adhesion signaling at the cell membrane. These membrane receptors sit in the phospholipid bilayer with hydrophobic regions that match the membrane interior. They provide attachment sites for outside signals such as hormones and growth factors. When these effectors bind and become active, integrins can start response pathways inside the cell. Some integrin-driven pathways support cell growth and help cells survive. The signal begins at the membrane, but G-proteins and...

anchoring junctions

Cell Adhesion in Anchoring Junctions

Anchoring junctions are multiprotein complexes that help cells connect to other cells and to the extracellular matrix. They sit on the lateral and basal surfaces of cells. These junctions create strong, flexible links that help maintain tissue stability and integrity. Focal adhesions often form when cells interact with the extracellular matrix, or ECM, substrata. These contacts can start signal transduction through kinase cascades and other pathways. Together, these junctions help cells stay...

cell-matrix's response to mechanical forces

cell-matrix-s-response-to-mechanical-forces

Focal Adhesions and Cell Mechanics

Focal adhesions help animal cells connect to the extracellular matrix and sense mechanical forces. The extracellular matrix, or ECM, sits outside cells and helps tissues withstand stress. It also sends signals from outside the cell to the inside. The ECM is large and its makeup changes from one tissue to another. In loose connective tissue, reticular fibers and ground substance form the ECM. In bone tissue, collagen and bone minerals make up the ECM. Anchoring junctions hold a cell to the...

key terms and concepts

Learn how integrins use outside-in and inside-out signaling to change shape, strengthen adhesion, and support cell migration and survival.

How Integrins Link Cells to Their Environment | JoVE K12

cell biology

JoVE Core Cell Biology illustrates complex cellular processes in easy-to-understand yet comprehensive animated video lessons. This collection focuses on the essential components and functions of cells, including organelles and membranes, cellular transport, and cell energetics. It is complemented by scientist-in-action videos that demonstrate the application of cell biology in real-world research experiments.

How Integrins Link Cells to Their Environment

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