Cell Adhesion Flashcards
What are the classes of adhesive structures in the cell?
- Cellular adhesion Molecules
- Extracellualr Matrix
- Cellular Junction Complexes
What are the classes of cellular adhesion molecules?
- Cadherins
-IgCAMS (immunoglobulin superfamily (IgSF) - Selectins
-Integrins
What role do transmembrane proteins play in cell-to-cell recognition and adhesion?
Adhesion and reception rely on the transmembrane proteins, which dynamically ASSEMBLE and DISASSEMBLE in the membrane.
This process coordinated with other major cellular processes such as signaling,movement, and proliferation.
How do cells interact through different adhesive proteins?
- CAM bind to the same type of molecule of one cell on another cell
- CAM binds one cell to a different type of molecule on another cell
What are the purposes of Cadherins?
1.Responsible for strong Ca2+ dependent cell to cell adhesions
2.play a key role in maintaining tissue structure and integrity
3.its expression is essential for proper embryonic tissue development
What is the structure of Cadherins? (Extracellular to intracellular)
-are 700-750 amino acid glycoproteins with a single transmembrane domain
-five cadherin repeats in the extracellular domain
-Ca2+ binding between the repeats provides rigidity to the structure
-structure becomes floppy in absence of calcium
-floppy structure is susceptible to proteolytic degradation
- 2 sets of Cadherins repeats come togther to form a homodimer
-the dimerized cadherin repeats in the extracellular region form the homophilic binding domain for these adhesion molecules
-the cystolic domain anchors the cadherin diner to the actin cell cortex
-accessory proteins called catenins (a-,b-, and p120) facilitate this interaction with the cell cytoskeleton
-
How does cadherin adhere to the cell?
-utilizing homophilic binding
-the cadherin from one cell binds the cadherin of an adjacent cell
-adhesion results from the formation of a TRANS-DIMER between the adjacent cells
What are types of Cadherins?
- E-Cadherins (epithelial cadherin) is primarily found in epithelial tissues and is crucial for the formation of adherens junctions
2.N-Cadherins (neural cadherin) is expressed in neurons and other tissues like muscle and play a role in tissue morphogenesis and signalling
- P-Cadherins (placental cadherin) is found in the placenta and skin
Note: they bind to their matching subtype- E->E
What are and the purposes of IgSF CAMs?
-One more domains which resemble those found in Immunoglobulins (antibody)
-capable of forming both homophilic and heterophilic interactions
-support a broad range of cellular interactions (cell recognition, neural network formation,and cellular signalling)
What is the structure of IgCAMs?
-the extracellular domain contains the Ig-like binding domains
-are classified into variable (V) domains and constant (C) domains
-number varies per cell
-stabilized by disulfide bonds
-fibronectin domains anchor to the transmembrane region and serve as SPACERS
-size exclusion mechanism for binding specificity
-most are transmembrane proteins
-some are bound to cell membranes via a GPI anchor
-GPI anchor consists of a glycan core of inositol, GlcNAc, and Mannose bound to a phosphatidylamine linker
How do IgCAMs function?
-can adhere through homophilic to another IgCAMs on an adjacent cell
- or heterophilic to an interstitial on an adjacent cell
What are the types of IgCAMs?
NCAMS
Neural Adhesion Molecules: primarily found in the nervous system, play a crucial role in neural development, synaptic plasticity, and cell migration
ICAMS: intracellular adhesion molecules
Found on endothelial cells, are critical for immune cell trafficking and leukocyte adhesion during immune responses
VCAMS:vascular cell adhesion molecules
Found in vascular endothelial cells, are in combed in immune cell adhesion and plays in roles in inflammation and vascular biology
What are selectins?
Include characteristics
-cell surface glycan structures
-heterophilic binding
-mediated by selectins
-more transient and less stable
How do selectins function?
-binding of carbohydrate targets is Ca2+ dependent
What is the structure of a selectin?
-Extracellular domains of selectins are linearly arranged
-composed of three regions:
The short consensus repeats (SCRs) 🪄
EGF domain🎏
Lectin domain🎈
🪄- number of SCRs depend on type of selectin:
E-type has SIX repeats
L-type has two repeats
P-type has nine repeats
-the repeats regulate the length of the extracellular domain which facilitates spatial positioning for ligand binding
🎏epidermal growth factor resembles EGF proteins structurally
🎏provides stability to the selectin
🎏provides flexibility for the lectin domain to facilitate optimal ligand interaction
🎈is the N terminal region of the selectin CAM
🎈is the binding domain for selectins
🎈dependent on Ca2+
🎈weak bind affinity
🎈heterophilic binding to sialylated and fucosylated glycoproteins, proteoglycans, glycolipids on target cells
How do selectins bind to the cell
(Mechanism)
-modular structure allows rolling adhesion
-leukocytes bind transiently to glycan structures on endothelial cells and “roll” along the vessel wall
-rolling is crucial for slowing down leukocytes and enabling firm adhesion and discharging at sites of inflammation
-the calcium dependent lectin domain enables selectins to quickly bind and release their ligands
Types of selectins
•L-selectin (Luekocyte selectin): found on leukocytes, it plays a role in lymphocyte homing: basically helping lymphocytes get to their correct destination. This will initiate luekocyte rolling on endothelial surfaces (blood vessels)
•E-selectin (endothelial selectin) during inflammation; and mediates the recruitment of leukocytes to sites of tissue injury
•P-selectin (platelet selectin) found on platelets and endothelial cells mediates the early recruitment of leukocytes to inflamed or injured tissue
What are integrins?
-are heterodimeric transmembrane proteins containing both a and B subunits
Purpose and characteristics of Integrins
-primary role in cell adhesion to the extracellular matrix (ECM)
-Integrins bind is dependent upon the prescence of a divalent cation frequently Ca2+ but Mg2+ is also used
-essential for cell migration, intracellular signal transduction, tissue integrity, and mechanical signaling
What’s the extracellular matrix (ECM)?
-refers to the region surrounding cells in a multicellular organism
What are the common elements of a ECM?
- Structural proteins: to provide strength and flexibility to the ECM (collagen & elastin)
2.Protein: Polysaccharide Complexes- a network of proteoglycans, glycoaminoglycans (GAGs)
3.Adhesive Glycoproteins: to facilitate cell attachment to the ECM, fibronectins and laminins
What is the Structure of ECMs?
-collagen fibers provide enormous strength to the ECM
-each collagen protein molecule is 3 polypeptide chains wound togther
-collagen fibers are first woven into collagen fibrils
-collagen fibrils wove togther to become collagen fibers
What is the functionality of the ECM Proteins?
-formed of elastic fibers made of elastin proteins
-tension causes the fibers to stretch
-elastic recoil and reformation when tension is released
ECM Protein-Structure of Polysaccharide Complexes
-proteoglycans consist of a protein core with several branches of GAGs
• chondroitin sulfate, keratan sulfate
-may be furthermore supported by a core of Hyaluronate
-attracts both water and cations to form a gelatinous mix
-collagen and elastic fibers embedded within matrix
ECM- structure of adhesive glycoproteins
-Finronectin is an adhesive glycoproteins in the ECM
-serves as the main intermediary to connect cell surfaces to ECM proeins
-fibronectin linked to cell movements through the ECM
•uncontrolled movement in cancer cells
-laminins are adhesive glycoproteins
-present larger numbers in thin ECM layer associated with epithelial cells
-layer known as basal lamina
•forms structural support and permeability layer
What is the structure of Integrins?
-the extracellular domain consists of a both an a and B subunit
-these subunits come together to form the ECM binding site
-the a subunit coordinates with Ca2+ or Mg2+ for structural stability
-there are 18 a subunits and 8 B subunits
-specific combination of subunits provide binding specificity
-the cytoplasmic tails interact with the proteins TALIN and VINICULIN to link Integrins to the actin cytoskeleton
Integrin Structure- appearance
-are heterosimers that can exist in an extended active state for ligand binding or a bent inactive state
-activity of Integrins are governed by intracellular and extracellular signals
How do Integrins function in mammalian cell culture to mediate cell adhesion?
Integrins mediates cell adhesion by BINDING TO THE EXTRACELLULAR MATRIX-mimicking materials coated on culture flasks. These coatings can be made of actual ECM proteins or synthetic compounds.
What are common flask coatings?
- COLLAGEN: often used to promote adhesion in cell types that naturally interact with collagen-rich environments,
such as Fibroblasts and epithelial cells
2.FIBRONECTIN: supports adhesion for a wide variety of cell types, including endothelial cells and muscle cells
Fibronectin is known to enhance cell spreading, migration, and differentiation
3.LAMININ: especially beneficial for epithelial, endothelial, and neural cells.
It promotes strong adhesion and helps maintain a more natural cellular morphology
4.POLY-L-lysine (PLL):
Synthetic polymer carries a positive charge, promoting adhesion of cells, especially neuronal and glial cells, to the negatively charged surface of the culture vessel.
It provides a supportive surface but DOES NOT engage in the same biological signaling as ECM proteins.
Additional Cultural flask coatings…
