Name: how adherens junctions sense force
Uploaded: 2023-04-30T12:28:30.000Z
Duration: 1 min 26 s
Channel: JoVE

רקמות כמו העור ואפיתל המעי חוות כל הזמן כוחות מכניים חיצוניים כגון צביטה או מתיחה.
הצמתים הנצמדים שמעגנים את תאי האפיתל הללו יחד יכולים להשתנות באופן דינמי בתגובה למתח מכני כזה. המרה זו של גירויים מכניים לשינויים ביוכימיים נקראת מכנוטרנסדוקציה.
בתאים אלה, הצמתים הנצמדים יוצרים אזור התקשרות רציף – חגורת ההדבקה – הכולל אשכולות גדולים של קדהרינים, קטנינים וצרורות כיווץ אקטומיוזינים.
האלפא-קטנין בצמתים אלה פועלים כחלבונים מכנו-סנסוריים המשנים קונפורמציה בתגובה למתח מכני.
כאשר כוחות כיווץ מוגברים מושכים את חוטי האקטין (actin filaments), האלפא-קטנין משתנה מהקונפורמציה המקופלת לקונפורמציה הפרושה.
התפתחות זו פותחת אתר קשירה מסתורי לווינקולין, חלבון קושר ציטו-שלד שנותר בצורתו הסגורה והלא פעילה בציטופלסמה.
עם קשירת אלפא-קטנין, וינקולין משנה את הקונפורמציה לצורתו הפתוחה והפעילה.
הוינקולין הפעיל מקדם גיוס חוטי אקטין נוספים לאתר, ובכך מחזק את הצומת ומפזר את הכוח על פני התאים.

<ol>
	<li>Charras, Guillaume, ו Alpha S. Yap. "כוחות מתיחה ומכנוטרנסדוקציה בצמתים תא-תא". ביולוגיה נוכחית 28.8 (2018): R445-R457.</li>
	<li>גולדמן, וולפגנג ה. "תפקיד וינקולין במכנוטרנסדוקציה תאית". ביולוגיה של התא הבינלאומי 40.3 (2016): 241-256.</li>
	<li>פינהיירו, דיאנה ויוהנס בלאיצ'ה. "כוח מכני מונע על ידי remodeling צומת ודינמיקה אפיתל." תא התפתחותי 47.1 (2018): 3-19.</li>
</ol>

תגובת מתח בצמתי אדהרנס

Tension Response at Adherens Junctions

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צמתי אדהרנס המעגנים תאים יחד הם קומפלקסים מרובי חלבונים המסתגלים באופן דינמי לגירויים מכניים כמו כוחות מתיחה ומתח גזירה. חלבונים מכנו-סנסוריים בצמתים אלה יכולים לחוש בגירויים מכניים כאלה ולעבור שינוי במבנה שלהם, וכתוצאה מכך לתפקוד שונה - תהליך הנקרא מכנוטרנסדוקציה.

α-קטינין כחלבון מכנו-סנסורי

ה-α-קטינין של צמתי אדהרנס הוא חלבון אלוסטרי בעל שלושה תחומי VH (הומולוגיה של וינקולין) שיכולים לקשור חלבונים קושרי אקטין שונים כמו וינקולין, אפדין ו-α-אקטינין. בתנאים רגילים, ה-α-קטינין מקופל, ותחומי הקישור של VH אלה אינם נגישים. ה-N-טרמינל מעוגן ל-β-קטינין, וקצה ה-C-טרמינל קשור לשלד האקטומיוזין. כאשר כוח המתיחה הפנימי גדל ומיוזין II מושך בחוט האקטין, ה-α-קטינין הקשור נפרש, ומתחמי ה-VH שלו הופכים זמינים לקישור.

תפקידו של וינקולין במכנו-טרנסדוקציה

וינקולין הוא חלבון דינמי נוסף עם מתחם ראש וזנב המחוברים לו אזור צוואר גמיש. בצורתו הלא פעילה, מתחמי הראש והזנב מקיימים אינטראקציה זה עם זה, ומונעים את הקישור של חלבונים אחרים. עם זאת, כאשר מתחם ה-VH החשוף של α-קטינין קושר את מתחם ראש הוינקולין, החלבון משתנה למבנה פתוח. מתחם הזנב החופשי יכול כעת לאגד אקטין ולגייס עוד חוטי אקטין לצומת זה. אזור הצוואר הפתוח קושר גם חלבונים שונים המווסתים פילמור אקטין, כמו Arp2/3, ובכך מארגן מחדש באופן דינמי את שלד האקטין בתגובה ללחץ מכני.
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הצמתים הנצמדים המעגנים תאים יחד הם קומפלקסים רב-חלבוניים המסתגלים באופן דינמי לגירויים מכניים כגון כוחות מתיחה ו...

Education

JoVE Core

Cell Biology

ביולוגיה של התא

Unit 1

יחידה 1

Cell-Cell Interactions

אינטראקציות בין תאים

KEY TERMS AND CONCEPTS

מונחים ומושגים מרכזיים

how adherens junctions sense force

Adherens junctions help cells stay attached while they respond to mechanical force. These multi-protein complexes can adapt to tensile force and shear stress. When the force changes, mechanosensory proteins in the junction can change shape. This process is called mechanotransduction.

Alpha-catenin is one of the main force-sensing proteins in adherens junctions. It is an allosteric protein, which means its shape affects how it works. Alpha-catenin has three VH, or vinculin homology, domains that can bind actin-binding proteins such as vinculin, afadin, and alpha-actinin. Under normal conditions, alpha-catenin is folded, so these VH binding domains stay hidden.

The N-terminal end of alpha-catenin is attached to beta-catenin. Its C-terminal end is linked to the actomyosin cytoskeleton. When internal tensile force increases, myosin II pulls on the actin filament. This pull makes alpha-catenin unfold. Once it opens, its VH domains become available for binding.

Vinculin also helps the junction respond to force. It has a head domain and a tail domain joined by a flexible neck region. In its inactive form, the head and tail interact with each other, which blocks other proteins from binding. When the exposed VH domain of alpha-catenin binds the vinculin head domain, vinculin changes into an open shape.

In the open form, vinculin can use its tail domain to bind actin and recruit more actin filaments to the junction. The open neck region can also bind proteins that control actin polymerization, such as Arp2/3. Together, these changes help reorganize the actin cytoskeleton in response to mechanical stress.

How Adherens Junctions Sense Force

cell adhesion molecules - types and functions

cell-adhesion-molecules-types-and-functions

Cell Adhesion Molecules in Tissues

Cell adhesion molecules help cells stick together and work as part of a tissue. They give multicellular organisms physical strength and also help cells send signals across the plasma membrane. These proteins are important for coordinated activity in tissues and organ systems. CAMs are grouped into four main families: integrins, cadherins, selectins, and immunoglobulin-like CAMs, or IgCAMs. Each family supports cell interactions in a different way. Some CAMs help cells attach firmly, while...

structure of cadherins

Cadherins in Cell Junctions and Disease

Cadherins are cell adhesion proteins that help cells stick together and build tissues. Their name comes from their calcium-dependent binding. Early examples were named E-cadherin, P-cadherin, and N-cadherin after the epithelial, placental, and neuronal cells where they were first found. Classical cadherins share similar sequences and structures. Other cadherins, including those involved in cell signaling, are grouped as non-classical cadherins. This diversity comes from multiple cadherin genes...

cadherins in tissue organization

Cadherins Guide Cell Sorting in Tissues

Cadherins help cells sort into the right tissues during development. They are a large superfamily of cell adhesion molecules, with more than 180 variants. Different tissues express specific cadherin combinations, which helps cells recognize and stick to the right neighbors. Cadherins usually bind to the same or a closely related cadherin on another cell. This is called homophilic binding. Because of this matching behavior, cells of the same type tend to group together and form clusters that...

catenins

Catenins in Cell Junctions and Signaling

Catenins help cells stay connected and also support signaling inside the body. These proteins act as linker proteins in cell junction complexes because they have multiple binding domains and flexible structures. Most catenins contain a protein sequence called the armadillo repeat, so they are also known as armadillo proteins. Alpha-catenin is the main exception. Catenins bind to cell adhesion molecules such as cadherins. They then connect cadherins to cytoskeletal proteins, and the exact link...

selectins

Selectins in Immune Cell Capture

Selectins help cells make short, temporary contacts during immune responses. They are cell adhesion molecules that bind carbohydrate ligands on other cells. These rod-like proteins have a long outside region and end in a lectin domain, which binds carbohydrates only when calcium ions are present. Three main selectins are known: L-selectin, P-selectin, and E-selectin. Their names reflect where they are found and how long they are. This tissue specificity helps explain why selectins act in...

immunoglobulin-like cell adhesion molecules

immunoglobulin-like-cell-adhesion-molecules

Ig-CAMs in Neural Growth and Disease

Ig-CAMs, or immunoglobulin-like cell adhesion molecules, are cell surface glycoproteins in the immunoglobulin superfamily. They contain immunoglobulin domains, and some also have fibronectin type III domains. Their Ig domains can be glycosylated to different degrees. These molecules can bind to the same kind of Ig-CAM or to other ligands, such as integrins. Most Ig-CAMs help cells stick together only for a short time. The nectin class is different because it helps form stable junctions,...

overview of cell-cell junctions

Cell Junctions in Tissues

Cell junctions help hold tissues together and let neighboring cells communicate. In multicellular organisms, the three-dimensional shape of tissues depends on interactions between cells and the extracellular matrix. Cell-cell junctions are specialized structures made of multi-protein complexes on one cell that connect with similar complexes on another cell. These junctions are grouped into three main types based on function: occluding, anchoring, and gap junctions. Tight junctions, also called...

adherens junctions

Cell Adhesion in Tissues and Infection

Adherens junctions are strong cell-to-cell anchors that help tissues stay connected. These anchoring junctions work with desmosomes, another type of junction that holds adjacent cells together. In many epithelial and endothelial tissues, adherens junctions form a continuous adhesion belt. In heart muscle, they often appear as clusters that help cells work together for coordinated contraction. Adherens junctions are also dynamic, especially in the cells that line blood vessels. These...

tension response at adherens junctions

Adherens junctions help cells stay attached while they respond to mechanical force. These multi-protein complexes can adapt to tensile force and shear stress. When the force changes, mechanosensory proteins in the junction can change shape. This process is called mechanotransduction. Alpha-catenin is one of the main force-sensing proteins in adherens junctions. It is an allosteric protein, which means its shape affects how it works. Alpha-catenin has three VH, or vinculin homology, domains...

desmosomes

Desmosomes and Cell Anchoring

Desmosomes are cell junctions that anchor cells together. They are button-like structures that create an interlinked network of intermediate filaments across cells. This strong link helps tissues resist mechanical stress and maintain tissue integrity. Desmosomes are built from multiple proteins. Their core includes desmosomal cadherins, which are adhesion proteins that bind to cadherins on neighboring cells. The two desmosomal cadherins are desmogleins and desmocollins. These transmembrane...

tight junctions

Tight Junction Proteins and Cell Barriers

Tight junction proteins form seals between neighboring cells. These molecular barriers help stop fluids, ions, and other small solutes from leaking across body cavities and tissue compartments in multicellular organisms. They are an important part of cell barriers in places where controlled movement matters. The main tight junction proteins are claudin and occludin. Other proteins include tricellulin and JAM, which stands for junctional adhesion molecule. Most of these proteins are 4-pass...

gap junctions

Cell Communication Through Gap Junctions

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key terms and concepts

Learn how adherens junctions use alpha-catenin and vinculin to sense tension, unfold, and reorganize actin during mechanotransduction.

How Adherens Junctions Sense Force | 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 Adherens Junctions Sense Force

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