Lecture 2 Cell Adhesion Molecules and Junctional Complexes Flashcards
Basement membrane
Separates an epithelial layer from its connective tissue support
Exception is capillaries, no connective tissue
Characteristics of the basement membrane
50-80 nm thick
Two components 1. basal lamina 2. reticular lamina
Two components of basement membrane
- Basal lamina
2. Reticular lamina
Basal lamina
Sits on reticular lamina
Produced by the epithelium
Reticular lamina
Produced by the connective tissue
Basement membrane is composed of
Intracellular matrix
4 Components of the basal lamina
- Laminin
- Type IV collagen
- Entactin (nidogen)
- Proteoglycans
Laminin
Component of basal lamina
Made of 3 polypeptide chains
-alpha, beta and gamma
Binding sites for entactin and proteoglycans
Type IV Collagen
Component of basal lamina
Does not form fibrils like type I collagen
This is collagen produced by epithelial cells, unlike type I collagen which is secreted by fibroblasts
Collagen
Connective tissue
most ubiquitous protein in your protein in your body (tendons/ligaments)
20 different kinds, made by 20 different genes
Fibronectin
How we hold things together Made up of two polypeptide chains cross-linked by disulfide bonds Has binding sites for -Heparin -Integrins -Collagen -Fibrin
4 Things Fibronectin has binding sites for
- Heparin
- Integrins
- Collagen
- Fibrin
Cell Adhesion Molecules
Depending on the need for calcium in their interactions with other molecules, cell adhesion molecules are divided into two groups
- Calcium dependent
- Calcium independent
Calcium Dependent Cell Adhesion Moleucles
Cadherins
Selectins
Calcium Independent Cell Adhesion Molecules
Integrins
Immunoglobulin superfamily molecules
Two groups of CAMs
Calcium dependent
Calcium independent
3 Types of Cadherins
- E-Cadherins
- N-Cadherins
- P-Cadherins
E-Cadherins
Most common type of cadherins
They are found in epithelial tissues
form diners
Most common type of cadherin
E-Cadherin
Dimers
Generic term for two molecules held together
Loss of e-cadherins
Associated with invasive behavior of tumor cells. Occur because of mutations, not all tumors are invasive
E-Cadherin dimers
HVA binding face
Dimers between epithelial tissues form homophilic interactions
Loss of e-cadherins is associated with invasive behavior of tumor cells
N-Cadherins
These are found in nerve tissues
P-Caderins
Found in placenta
Catenins
Cytoplasmic domains of cadherins are linked to actin through catenins
Alpha Catenin
(sounds like actin)
Bind directly to actin
Beta Catenin
Bind to cadherin and to y-catenin/plakoglobin
Involved in colorectal carcinogenesis
Characteristics of selectins
- Selectins bind to carbohydrates, therefore they belong to the lectin group
- Selectins are involved int he movement of leukocytes from blood to tissues (extravasation)
Extravasation
Selectins are involved in the movement of leukocytes from blood to tissues
Leukocytes
Make in bone marrow involved in immune response
3 Classes of Selectins
- P-selectins
- E-selectins
- L-selectins
P-Selectins
Platelets (surface of)
E-Selectins
Activated Endothelial cells
-during inflammatory process, they are activated
L-Selectins
Leukocytes
Integrins
Calcium independent
Mainly involved in cell-extracellular matrix interactions
Integrins bind to both the extracellular matrix and to the cytoskeleton
Integrins are heterodimers
The extracellular domains of integrins bind to molecules in the basement membrane
Integrins bind to both
The extracellular matrix and to the cytoskeleton
Heterodimers
Different types of molecules involved
Integrins are these
2 major molecules in basement membrane
- Fibronectin
2. Laminin
Integrins interact with
the RGD (Arg-Gly-Asp) sequence in fibronectin and laminin -if sequence is disrupted, they won't bind
Laminin and fibronectin in the basement membrane interact with
Collagen (including type IV)
Heparan sulfate proteoglycans
Entactin (nidogen)
Integrin Heterodimers
Each consists of one alpha subunit (17 kinds) and one beta subunit (8 kinds) *combined in different ways
The cytoplasmic domain of the beta subunit is linked to actin filaments via connecting proteins
Connection proteins include: - Talin - Vinculin - Alpha-actinin
3 Connecting proteins include
- Talin
- Vinculin
- Alpha-actinin
Characteristics of the Immunoglobulin superfamily
Members of this family possess an extracellular segment with one or more folded domains characteristic of immunoglobulins
Members of the Ig-superfamily
N-CAM
I-CAM-1 and I-CAM-2
N-CAM
Member of Ig-superfamily
These are neural adhesion molecules
They mediate both homophilic and heterophilic interactions
I-CAM-1
Facilitates transoendothelial migration of leukocytes
Adherens
Bind cells together. Can bind cells to the basement lamina too
Type of junction
Designed to anchor cells together
Can be found on the basolateral surfaces of epithelial cells
Occludens
Junctional complexes that establish an impermeable barrier between adjacent cells, especially epithelial cells, that prevents paracellular transport.