Cell adhesion molecules

Download Cell adhesion molecules

Post on 21-Apr-2017

82 views

Category:

Health & Medicine

0 download

Embed Size (px)

TRANSCRIPT

  • CELL ADHESION MOLECULES Nahla Imbarak Teaching Assistant of Histology and Cell Biology

    Faculty of Medicine- Suez Canal University

  • Introduction:

    Cell adhesion is the ability of a single cell to stick to another cell or an extracellular matrix (ECM). Cell adhesion molecules are proteins that help cell stick to each other and to the surroundings.

    Adhesion plays an integral role in cell communication and regulation, and is of fundamental importance in the development and maintenance of tissues.

    Cell adhesion is involved in stimulating signals that regulate cell differentiation, cell cycle, cell migration, and cell survival.

    According to the cell adhesion model, the more a cell sticks the more it shows the greater number of chemical bonds it has on its surface.

  • Introduction

    Changes in cell adhesion can be the defining event in a

    wide range of diseases including arthritis, atherosclerosis,

    osteoporosis, and cancer .

    Cell adhesiveness is generally reduced in human cancers.

    Reduced intercellular adhesiveness allows cancer cells to

    disobey the social order, resulting in destruction of

    histological structure, which may be related to the invasive

    and metastatic potential.

  • Integral membrane protein parts:

    Integral membrane protein embedded in the phospholipid

    bilayer , and has free major portions.

    The portion of the protein that spends the membrane, called

    trans- membrane region (TMR).

    The extracellular domain of the protein (ECD).

    The intracellular domain of the protein (ICD).

  • Types of cell adhesion molecules (CAMs) binding:

    Homophilic binding:

    If the cell adhesion molecules between two neighboring cells are the identical. (Cadherin-Cadherin)

    Hetrophilic binding:

    If the cell adhesion molecules between two neighboring cell are not identical. (Selectin-Mucin)

  • Hetrophilic binding:

    If the cell adhesion molecules bind between a cell and the

    extracellular matrix meshwork=

    collagen fibers

    fibronectin protein Dimer

    polysaccharides (heparin sulfate)

    Dense and wide binding

  • Cell adhesion molecules

    1. Immunoglobulin super family cell adhesion

    molecules

    2. Integrin

    3. Selectin

    4. Cadherin

  • IMMUNOGLOBULIN SUPER FAMILY

    CELL ADHESION MOLECULES

  • 1. Immunoglobulin super family cell adhesion

    molecules (IgSF CAMs):

    Structure:

    The trans-membrane region of all the IgSF-CAMs is a single

    alpha helix span the membrane. (one protein)

    Inside and outside we have extracellular domain.

    IgSF CAMs

  • Example: 1. Intercellular adhesion molecule-1

    (ICAM-1):

    Its is expressed in the apical membrane of

    endothelial cells (mainly capillary and post

    capillary venues).

    When there is an invading pathogen, the

    endothelial cells become activated and will

    express ICAM-1 on their surfaces.

    ICAM-1 will bind to cell adhesion molecule

    LFA-1 (Lymphocyte function associated -1,

    Integrin molecule) expressed on monocytes.

    Monocytes will move across the endothelial

    cells to the interstitial space to differentiate to

    macrophage.

    IgSF CAMs

  • 2. Vascular cell adhesion molecule-1

    (VCAM-1):

    Its is expressed in the apical membrane of

    endothelial cells.

    When there is an invading pathogen, the

    endothelial cells become activated and will

    express VCAM-1 on their surfaces.

    VCAM-1 will bind to cell adhesion molecule

    VLA-4 (very late antigen-4, Integrin molecule)

    expressed on monocytes.

    Monocytes will move across the endothelial cells

    to the interstitial space to differentiate to

    macrophage.

    Heterophilic binding

    IgSF CAMs

  • 3. Platelet endothelial cell adhesion-1 (PCAM-1)= CD31:

    Endothelial cells posses three types of junctions:

    I. Tight junction

    II. Adherent junction

    III. Two PCAM-1 protein on the opposing endothelial cell membranes.

    ( Homophilic binding )

    IgSF CAMs

  • Integrin

  • 2. Integrin:

    Structure:

    The protein is formed of two subunits, and subunit.

    (there are 18 and 8 subunit type, however, only 24 types

    found in human body )

    Has a large extracellular domain.

    Single membrane spanning helix.

    A very small intracellular domain.

    Integrin

  • Example:

    1. Lymphocyte function-associated antigen1(LFA-1):

    LFA-1= 11 2 = L 2

    Found on the surface of all leucocytes and mainly on the

    monocyte.

    In the inflammatory state, the endothelial cells starts to

    express the ICAM-1 on its surface to bind to LFA-1 of the

    monocytes > differentiate to macrophage in the interstitial

    space.

    2. Very late antigen-4 (VLA-4):

    VLA-4 = 4 1

    Found on the surface of the monocyte.

    In the inflammatory state, VLA-4 binds to VCAM-1.

    Integrin

  • 3. Integrin bind directly to collagen:

    1 1

    2 1

    4. Integrin bind indirectly to collagen:

    First bind to Fibronectin

    5 1

    Integrin

  • 5. Integrin fix epithelial cells to the basment

    membrane:

    The BM is formed of two layer of CT separated by space.

    The endothelial cells sit on the basal lamina of the BM.

    Anchoring integrin: 3 1 - 6 1 - 7 1

    Integrin

  • Selectin

  • 3. Selectins:

    Example:

    1. P- Selectin: Found on the endothelial cells to help the

    recruitment of the neutrophils, P-Selectin

    glycoprotein ligand 1, type 1

    activation (induced by histamine and

    induced in minutes)

    2. E-Selectin:

    Found on the endothelial cells and binds

    to Sialyl-Lewis X found always on the

    surface of the neutrophil type 2

    activation (takes hours)

  • 3. L-Selectin:

    The high endothelial cells allows the nave T lymphocytes to move from

    the blood into lymph nodes and back out.

    Nave T-lymphocytes have on their

    surface the L-Selectin that binds to

    GLYCAM-1 on the high endothelial cells

    movement of the lymphocyte to the

    Lymph node.

    The unusual cuboidal endothelial cells (EC) have

    lighter-staining nuclei than the lymphocytes (L)

    which are in the process of migrating from the

    lumen (bloodstream) into the diffuse cortex (DC)

    of the node.

    Selectin

  • Cadherin

  • 4. Cadherin superfamily:

    Extra cellular cadherin domain range from (1-34) domains.

    All cadherin are a trans membrane protein except T-cadherin.

    Types of Cadherin:

    1. Type I classical cadherin

    2. Type II atypical cadherin

    3. Truncated cadherin

    4. Desmosomal cadherin

    5. Flamingo cadherin

    6. Proto cadherin

    7. Others

    Cadherin

  • 1. T- cadherin is completely outside the cell membrane

    and attached to it by a lipid called Glycosyl

    phosphatidylinositol (GPI).

    Types of Cadherin: Cadherin

  • 2. Type I classical cadherin:

    It produce cell to cell direct connection.

    (Adherent Junction)

    Example:

    E- Cadherin: found in the epithelial cells

    N - Cadherin: found in the neuron, muscle tissue

    P - Cadherin : found in the placenta, epidermis

    Structure:

    They all have 5 extracellular cadherin domain ended

    with amino terminal NH2.

    The N terminal of the Extra cadherin domain will bind

    to the neighboring N terminal of the EC domain.

    The binding is dependent to the extra cellular Ca ions

    Cadherin

  • The cytoplasmic terminal end binds to 2 proteins:

    1. P120 catanin

    2. - catinin + catinin

    catinin anchored the cadherin to the cytoskeleton actin filaments.

    E-cadherincatenin complex functions as a master molecule in regulating

    not only cell adhesion but also polarity, differentiation, migration,

    proliferation, and survival of epithelial cells.

    Cadherin

  • 3. Desmosomal Cadherin:

    Types:

    Desmocollin (1,2,3)

    Desmoglein (1,2,3,4)

    Structure:

    They all have 5 extracellular cadherin domain ended with NH2.

    (1 E anchor domain and 4 EC domains distally)

    The N terminal of the Extra cadherin domain will bind to the neighboring N

    terminal of the EC domain.

    The cytoplasmic terminal end binds to 2 proteins:

    1. Plakoglobin= catenin

    2. Plakophilin

    These two proteins will bind to desmoplakin intermediate filament (Keratin)

    The binding is dependent to the extra cellular Ca ions.

    Cadherin

  • The extracellular core allows water and ions flow in between the cells.

    E.g: Skin, Intestins

    Cadherin

  • Integrin and Ig Superfamily CAMs are Ca independent.

    Cadherin and Selectin are Ca dependent.

    Integrins participate in cell-matrix interaction while other

    CAMs participate in cell-cell interaction.

  • TYPES OF CELL JUNCTIONS

  • TYPES OF CELL JUNCTIONS

    Gap Junction

    Tight Junction

    1. Zona occludance

    2. Fascia occludance

    3. Macula occludance

    Adherence junction- Anchoring junction 1. Zona Adherence = Belt De