Cell-Cell and Cell-ECM Interactions Flashcards
What are cell junctions?
What are the 3 types?
Specialized structures on cell surface where you have specific structures which mediate binding of cells to each other or to the extracellular matrix.
There’s 3 types: Gap Junctions, Tight Junctions and Anchoring Junctions
What is the extracellular matrix (ECM)?
example proteins and function
A complex combination of proteins and polysaccharides
- secreted and assembled by cells into a network to hold cells and tissues together.
Function:
- anchoring and engulfing cells to maintain solid tissue 3D architecture
- determining biomechanical properties of the tissue (stiffness/elasticity, porosity, shape)
- controlling cellular porosity, survival, proliferation, differentiation and fate
- inhibiting/facilitating cell migration
- binding to and acting as a reservoir for growth factors
Proteins can be…
- hydrophilic (ex. Proteoglycans absorb water and provide tissue resiliency)
- structural (ex. Collagens provide strength and support)
- adhesive (ex. Fibronectins are recognized by cell-surface proteins==Integrins, to allow cell adhesion and migration). (ex. Laminins)
Gap junction
structure
function
example
- 6 connexins (transmembrane proteins) form a connexon
- allow passage of ions and SMALL molecules across channel for COMMUNICATION of the cytoplasm of adjacent cells
- functions:
- coordinate contraction of cardiac muscles
- coordinate muscular contraction waves in intestine (peristalsis)
=== integrate activities of individual cels into a functional unit - Ca2+ regulated channel….. high Ca=closed
How can you regulate the permeability of gap junctions?
regulated by posttranslational modification of connexins (e.g. phosphorylation)
+ sensitive to environmental conditions (ie, intracellular pH and Ca2+ concentrations, membrane potential.)
Tight junction
structure
function
What would you treat it with to destroy it?
a type of cell-cell junction between the plasma membrane of adjacent EPITHELIAL cells, binds them strongly together!
- involves thin bands/rows of Claudin, JAM, Occulin transmembrane proteins (they each have extracellular domains) that completely encircle each cell, and are in contact with bands on adjacent cell to make tight seal.
Functions as barriers that regulate the movement of water and solutes between epithelial layers
- can be destroyed by treatment of protease Trypsin
What are the four major families of CAMs that anchoring junctions use?
Cadherins, Ig superfamily, Integrins, Selectins
The cytoplasmic domains of these proteins are often associated with adapter proteins that link them to the cytoskeleton or to signalling pathways
Homophilic Interactions
- what are they?
- what CAMs are used?
Homophilic binding/interactions/cell-cell adhesions = interaction btwn same CAM on surface as neighbouring cell. (aka, two cadherins bound together)
Homophilic interactions use:
1) Cadherins = Calcium-dependent adherins == cells can adhere via Homo interactions only if Ca is present
2) Ig Superfamily – mediate Ca-INdependent adhesions
Cadherin
- Structure
- What two types of junctions are cadherin-based?
- How do they know once they’ve bound?
type of CAM that anchoring junctions = single transmembrane domain (outside cell) + cytosolic C-terminal tail that’s associated with cytoskeleton(inside cell). (depending on the cytoskeletal element, that determines function):
Forms 2 types of cadherin-based anchoring junctions:
- Adherens Junctions (btwn cells)
- Cadherin–Adaptor protein–Circumferential belt (F-actin-microfilament-based cell structure)–Cadherin
- Desmosomes (btwn cells or ECM)
- Cadherin—adaptor proteins– Intermediate Filaments (Keratin)– Cadherin
- for additional support
- the cells will know if they are linked to each other because the CAM link to the cytoskeleton will allow for cell signalling. (so these anchoring junctions are for attachment but also for cell signalling– see beta-catenin)
Types of Cadherins
E-Cadherin: in preimplantation embryos, and non-neural epithelial tissue
P-Cadherin: in trophoblast
N-Cadherin: in nervous system, lens, cardiac, and skeletal muscle
What is the function of ß-Catenin in relation to cell adhesion?
plays a dual role as a transcriptional activator and as a membrane-cytoskeleton linker protein:
- Mediates cytoskeletal attachment
- Serves as a signalling molecule , translocating to the nucleus and altering gene transcription in the Wnt signalling pathway.
Describe the surfaces of an epithelial cell lining the small intestine
Apical surface: surface facing lumen of intestine. Has microvilli/filopodia-like structures which increase surface area of the cell
Basal surface: in contact with ECM
Lateral surface: where cells interact with each other
Heterophilic Interactions
- what Cell Adhesion Molecules do they use?
= interactions of adjacent cells or ECM between different CAM. they use:
1) Integrin
B. Selectins: sit in plasma membrane; binds sugars on other side
Integrin
Structure
How is their binding specificity determined?
How do they bind?
= Heterodimeric transmembrane protein = composed of alpha and beta units (there are different types of subunits of these units). The different alpha-beta combos recognize specific substrates.
- ex. alpha1beta1 binds collagen
alpha5beta1 binds fibronectin
alpha6beta1 binds lamINin
- Integrin binds to core RGD AAs (Arg-Gly-Asp), but also require nearby synergy regions for specificity (aka, synergy regions are specific for different types of molecules)
- can be in inactive (bent) or active (extended) state – associated with transducing many cell signals
Extravasation – steps and changing cell interaction
Heterophilic interactions involving Selectins= glycan-binding proteins.
1. Resting cells: Leukocyte is in resting state travelling through blood (no P-selectin on endo cells)
2. Endothelium Activation and Rolling: Upon inflammation, endothelial cells are activated; and adhesion molecules (P-selectin and PAF) are expressed on their surface. P-selectin can bind to glycans on surface of leukocyte but the binding is not very strong, and so Rolling of leukocytes along the layer of endothelial cells because of weak selectin-mediated adhesion
3. Leukocyte Activation: the binding of PAF to PAF receptors on leukocytes activates neutrophils/leukocytes –> activates integrin beta2
4. Firm Adhesion: integrins bind ICAM creating a firm adhesion (ICAMs can be involved in homophilic and heterophilic interactions bc integrins can bind ICAM independently too)
5. Extravasation: now neutrophil/leukocyte can squeeze through layer of endothelial cells to get to pathogen in subendothelial tissue
Leukocyte went from blood —> tissue
What two anchoring junctions can integrins make?
Integrins connect cells to substratum (ECM) via integrin-based anchoring junctions…
A)Focal Adhesions – Integrin– actin filaments—Fibronectin (ECM)
- MIGRATING CELLS (or in culture dishes)
B)Hemidesmosomes – integrin–Keratin IFs –Laminin (ECM)
- ONLY in epithelial cells (NON-migrating cells)
- shape, rigidity, signalling
