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

Affinché una cellula possa migrare attraverso l'ECM, l'attacco della cellula all'ECM deve essere effettuato e rotto rapidamente.
Ciò è facilitato dalle integrine legate alla membrana che passano rapidamente da uno stato attivo, che forma attaccamenti, a uno stato inattivo che non lo fa.
Nella conformazione inattiva, le code del dimero dell'integrina sono bloccate insieme in modo compatto, impedendo all'integrina di legare le proteine della ECM o i filamenti del citoscheletro.
Le integrine possono essere attivate dall'esterno della cellula nel meccanismo "outside-in" o internamente nel meccanismo "inside-out".
Nel meccanismo "outside-in", le proteine della ECM come la fibronectina si legano al dominio extracellulare dell'integrina. Le code si sganciano e l'integrina passa da uno stato inattivo a uno stato attivo, esponendo i siti di legame per le proteine adattatrici citosoliche.
Al contrario, nel meccanismo "inside-out", le proteine adattatrici come la talina legano la catena beta citosolica dell'integrina, rompendo così il legame alfa-beta e separando le gambe dell'integrina. L'integrina attiva può ora legare le proteine della ECM.

<ol>
	<li>Ginsberg, M. H., Partridge, A., & Shattil, S. J. (2005). Regolazione delle integrine. Opinione attuale in biologia cellulare, 17(5), 509-516.</li>
	<li>David G. Menter, Raymond N. DuBois, "Prostaglandine nell'adesione, migrazione e invasione delle cellule tumorali", International Journal of Cell Biology, vol. 2012, ID articolo 723419, 21 pagine, 2012. <a href="https://doi.org/10.1155/2012/723419">https://doi.org/10.1155/2012/723419</a></li>
	<li>Campbell, ID, & Humphries, MJ (2011). Struttura, attivazione e interazioni delle integrine. Prospettive di Cold Spring Harbor in biologia, 3(3), a004994.</li>
</ol>

attivazione delle integrine

Activation of Integrins

Le integrine legano i ligandi e trasmettono informazioni dall'esterno della cellula all'interno o viceversa attraverso una "segnalazione outside-in" o "segnalazione inside-out".

Nella "segnalazione outside-in", i fattori esterni nello spazio extracellulare si legano ai siti di legame dei ligandi esposti sulle integrine. Questo fa sì che la proteina inattiva subisca un cambiamento conformazionale per diventare attiva. Le integrine sono spesso raggruppate sulla membrana cellulare. Eventi di legame del ligando ripetitivi e regolarmente distanziati forniscono uno stimolo efficace. Quando la cellula incontra vari segnali extracellulari, le integrine attivate influenzano le proprietà cellulari come la polarità cellulare, la struttura citoscheletrica, l'adesione, la migrazione, l'invasione, l'espressione genica, la sopravvivenza cellulare e la proliferazione.

La "segnalazione inside-out" dipende da attivatori intracellulari come proteine adattatrici del citoscheletro come talini o kindlin. I talini contengono siti di legame per i domini citosolici dell'integrina β, un sito di legame dell'actina C-terminale altamente conservato e un sito di legame della vinculina. Kindlin include siti di legame della coda citosolica dell'integrina β nei loro domini F3, domini di legame con la membrana e un C-terminale che interagisce con le integrine, le proteine adattatrici dell'actina o la chinasi legata all'integrina (ILK). Kindlin interagisce con il dominio citoplasmatico dell'integrina β e stabilizza lo stato attivato del complesso dell'integrina. La “segnalazione inside-out” può rafforzare l’adesione mediata dalle integrine con ligandi extracellulari, che trasferiscono la forza necessaria per la migrazione cellulare, l’invasione, l’assemblaggio dell’ECM e il rimodellamento.

Adattato dalla Sezione 9.1 Molecole di segnalazione e recettori cellulari, Openstax Biology per AP

Attivazione delle integrine

Le integrine legano i ligandi e trasmettono informazioni dall'esterno della cellula all'interno o viceversa attraverso una "segnalazione dall'esterno all'interno" o ...

Education

Didattica

JoVE Core

Cell Biology

Biologia cellulare

Unit 1

Unità 1

Cell-Matrix Interactions

Interazioni cellula-matrice

KEY TERMS AND CONCEPTS

TERMINI E CONCETTI CHIAVE

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

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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

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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

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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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