Name: cadherins in cell junctions and disease
Uploaded: 2023-04-30T11:54:59.000Z
Duration: 1 min 25 s
Channel: JoVE

קדהרינים הם משפחת על של מולקולות הידבקות תאים תלויות סידן או CAMs.
לכל הקאדרינים מבנה בסיסי הכולל תחום ציטוסולי קטן C-terminal, תחום טרנסממברנה יחיד, ומספר תחומים חוץ-תאיים של קדרין או EC.
תחומי EC אלה מקושרים זה לזה על ידי אזורי צירים גמישים, שלכל אחד מהם שלושה כיסים קושרי סידן.
כאשר יוני סידן נקשרים, הקדהרין הופך נוקשה, מה שמאפשר קשירת סיס וטרנס לקדהרינים אחרים.
בקשירת cis, cadherins על אותו תא יכול להיקשר אחד לשני וליצור אשכולות, בעוד האינטראקציה של תחומי EC של cadherins על תאים סמוכים גורמת trans-binding.
תחום N-terminal EC, הרחוק ביותר מהממברנה, הנקרא EC1, הוא בעל ידית ומבנה כיס. במהלך קשירת טרנס, הידית של EC1 אחד נכנסת לכיס של EC1 אחר בתא הסמוך.
זה גורם לקאדרינים מסוג אחד לקשור קאדרינים מאותו סוג, כריכה הומופילית.
למרות שהאינטראקציה בין זוג יחיד של קדהרינים חלשה יחסית, אשכולות הקדרין יכולים ליצור קשירת טרנס חזקה באופן קולקטיבי. קומפלקסים כאלה יוצרים צמתי תאים מעוגנים.

<ol>
	<li>שפירו, לורנס וויליאם וייס. "מבנה וביוכימיה של קדהרינים וקטנין". קולד ספרינג הארבור פרספקטיבות בביולוגיה 1.3 (2009): a003053.</li>
</ol>

מבנה הקדרינים

Structure of Cadherins

<div style="direction: rtl;">
הקדרינים היו אחת ממולקולות ההדבקה הראשונות של התא שהתגלו; המונח "קדהרינים" מבוסס על תכונות ההדבקה תלויות הסידן שלהם. הקדרינים הראשונים שהתגלו על תאי האפיתל, העצב והשלייה נקראו E-cadherin, P-cadherin ו-N-cadherin, בהתאמה. הקדהרינים הקלאסיים הללו חולקים רצף ודמיון מבניים. קדהרינים אחרים, כולל אלו המעורבים באיתות תאים, מקובצים לקדרינים לא קלאסיים. מגוון זה של קדהרינים נובע מגנים מרובים של קדהרין בגנום ומחבור RNA חלופי במהלך תעתוק.

קדהרינים בצמתי תאים

קדהרינים הם חלבונים טרנסממברנליים בעלי מספר מתחמי קישור חוץ-תאיים. התחום הציטוסולי שלהם קושר חלבוני קישור המתחברים לשלד התא. קדהרינים מתקבצים יחדיו על ממברנת הפלזמה על ידי קשירת cis, ויוצרים קומפלקסים גדולים ורב-חלבונים הנקראים חיבורי תאים. בעוד שקדהרינים קלאסיים כמו צורת E-cadherin נצמדים לצמתים, קדהרינים לא קלאסיים כמו דזמוגלאין ודסמקולין יוצרים צמתים דמוזומליים. חיבורי תאים אלה פועלים כדי להחזיק את התאים יחד ולספק חוזק מכני לרקמות, כגון האפיתל.

משמעות קלינית של קדהרינים

קדהרינים ממלאים תפקיד חיוני בהיצמדות תאים, יצירת רקמות ותקשורת בין-תאית. כתוצאה מכך, כל שינוי במבנה, בביטוי וביציבות שלהם יכול להתבטא במצבים קליניים. כאשר התאים מאבדים מגע עם תאים שכנים, הם יכולים להשתחרר מהרקמה ולפלוש לרקמות אחרות. אובדן היצמדות לתאים עקב מוטציות בגנים של קדהרין קשור לממאירות של גידולים, כמו אלה הנראים בתאים ממאירים בשד. פתוגנים משתמשים גם בקדהרינים כקולטנים כדי להצמד ולפלוש לתא המארח. לדוגמה, הקדהרין CDHR3 מתבטא מאוד באפיתל הריאות ומשמש כקולטן על ידי נגיף הרינו-C סוג-C (RV-C) הגורם להצטננות.
</div>

הקדהרינים היו אחת ממולקולות ההיצמדות התא הראשונות שהתגלו; המונח "cadherins" מבוסס על שלהם תלוי סידן ...

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

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 in the genome and from alternative RNA splicing during transcription.

Cadherins are transmembrane proteins. They have several extracellular binding domains and a cytosolic domain inside the cell. The cytosolic region binds linker proteins, which connect cadherins to the cytoskeleton. Cadherins also cluster on the plasma membrane through cis-binding, which helps form large protein complexes called cell junctions.

Classical cadherins such as E-cadherin form adherens junctions. Non-classical cadherins such as desmoglein and desmocollin form desmosomal junctions. These junctions hold cells together and give mechanical strength to tissues such as epithelium.

Cadherins are important for cell adhesion, tissue formation, and communication between cells. Changes in their structure, expression, or stability can lead to disease. When cells lose contact with neighboring cells, they may break free from the tissue and invade other tissues. Mutations in cadherin genes are linked to tumor malignancy, including in breast cancer cells. Some pathogens also use cadherins as receptors to attach to and enter host cells. One example is CDHR3, which is highly expressed in lung epithelium and is used by class-C rhinovirus, or RV-C, the virus that causes the common cold.

Cadherins in Cell Junctions and Disease

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 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

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...

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

Gap junctions let adjacent animal cells share small molecules, ions, and secondary messengers. These communication channels connect the cytoplasm of neighboring cells. They are built from many molecular channels, often from a few hundred to thousands in one junction. Each channel is made of two halves called connexon hemichannels. A connexon is a hexamer, meaning it is formed by six transmembrane connexin proteins. The six proteins arrange in a ring and create a pore in the center. One...

key terms and concepts

Learn how cadherins help cells stick together, form junctions, and support tissues, and how changes in cadherins can contribute to cancer and infection.

Cadherins in Cell Junctions and Disease | 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.

Cadherins in Cell Junctions and Disease

Description

Transcript

Tags