Cell adhesion and the ECM Flashcards
How is adhesion regulated?
Variable strength and duration of adhesions allows e.g. cell movements during development and tissue repair
What does adhesion depend upon?
Strength in numbers - velcro effect. Individual adhesion molecules may have a weak binding to their targets, but are clustered together to cellular junctions
Adherens junctions
Anchoring junction. Proteins are classical cadherins - transmembrane proteins with a characteristic repeat structure in their extracellular domain. The cadherin extracellular domains from neighbouring cells bind together to mediate adhesion.
What do cadherins require for adhesions?
Calcium ions. In the extracellular domain of the protein, flexible linkers between the cadherin repeats need to be stabilised to facilitate binding between cadherins form adjacent cells, requiring Ca2+ binding
How can crucial role of cadherins in adhesion be demonstrate by?
Experiments where E-cadherin (epithelial cells) expression was introduced to cell lines that do not normally express the protein. This resulted in Ca-dependent clustering of cells. Cadherin selectivity can be shown in experiments where E-cadherin expressing cells form separate clusters/structures from N-cadherin expressing cells
Connected to actin cytoskeleton
Intracellular adapter proteins mediate binding to actin cytoskeleton. Some variability in the adapters, but invariably, catenin proteins are involved. Loss of adherents junctions affects tissue integrity: invasive carcinomas often have lost E-cadherin expression
Desmosomes
Anchoring junction. Responsible for strong cell-cell adhesion mediated by desmosomal cadherins - demogleins and desmocoliins related to classical cadherins
What are desmosomes connected to?
Intermediate filaments. Different set of adapter proteins than those used in adherens junctions - form a dense plaque that can be seen in EM pictures
What can mutations in desmosomal proteins lead to?
Weak adhesion that can e.g. cause blistering and cell lysis in tissues.
Tight junctions
Form a seal between cells - cell membranes pressed close to each other, prevent movement of water and solutes in the space between cells. Therefore, they regulate transport through the epithelia. The binding is close but the adhesion is no strong in terms of contribution to tissue integrity
They restrict movement of membrane lipids in polarised cells from basolateral to apical surface
Rows of membrane proteins create a bubble wrap appearance of TJs
The proteins belong to occluding and claudin families that have several transmembrane domains generating extracellular loops that for non-covalent interactions with similar proteins on the adjacent cell. Adapted proteins such as ZO-I help clustering TJ adhesion proteins
Gap junctions
Form passageways between adjacent cells - present in most mammalian tissue
Composed of connexin proteins
Humans have 21 different genes for connexins with different sets of connexins expressed in different cell types
Heteromceric or homomeric connexin through the cell membrane
6 connexin proteins form
Joins a connexin on the membrane of the adjacent cell to form a gap junction
What molecules can pass through a gap junction?
Small molecules, up to about 2 kDa - ions, metabolites, small signalling proteins
What affects the permeability of a gap junction?
The diversity of connexins leads to differences in gap junction channel permeability. Permeability is also regulated by e.g. pH, calcium ion and protein phosphorylation
In neurons, gap junctions….
can facilitate rapid transmission of electric signals
In non-neuronal tissues, gap junctions…
can help integrate metabolic activities e.g. by passing second messenger proteins from one cell to another.
In heart muscles, gap junctions…
Help co-ordinate spreading of ionic signals that contribute to contraction of heart muscle
What can mutations of connexins cause?
At least 8 human diseases, including a form of deadness, a form of progressive degeneration of peripheral nerves and a condition with heart malformations
Plant cell wall adhesion
Do not have anchoring cell-cell junctions. Neighbouring plant cells joined by rigid cell wall. The primary cell wall is deposited after cell division and often reinforced by a secondary deposition. The key component is cellulose, a repeating polysaccharide. Cellulose fibres are embedded in the matrix of another polysaccharide, pectin, and glycoproteins
The cell wall allows diffusion of water and ions but is a barrier to cell-cell communication
Plasmodesmatata
Direct communication between adjacent plant cells. Plasmodesmata extend from one cell to another through the wall. Plasma membranes merge to form a continuous cannel – annulus.
Contain within the channel an extension of ER, desmotubule. Also, cytoskeletal filaments can continue through the plasmodesmata
The extracellular matrix
A complex arrangement of molecules filling spaces in between the cells, forming an organised structure. Mostly found in CT such as tendons, cartilage, bone or skin dermis. Diverse structures maybe created by different amounts and organisation of ECM components. Cells secrete ECM that is finally assume;ed outside the cell
ECM receptors
Cells have these on their plasma membrane, with the integral family of most importance
Function of the ECM
Provides physical strength and structural support and influences cell shape and behaviour e.g. proliferation and migration
ECM can participate in storage of some growth factors and other biologically stable active molecules
Involved in tissue repair mechanism and guidance of tissue interactions during embryonic development
