4MCB Cell Specialisations and Specialised Cells - Notes

Cell Specializations and Specialized Cells

Cell Junctions

• Most cells in multicellular organisms are in contact with other cells.
• A cell's immediate environment often consists of other cells.
• Physical connections between cells in a tissue determine the tissue's characteristics.
• Cell junctions coordinate the activities of individual cells, enabling systems to function as integrated wholes.
• These connections and interactions are fundamental and referred to as INTERCELLULAR JUNCTIONS.
• Cells rarely work in isolation.

Cell Adhesion Molecules (CAMs)

What are They?

• Mainly glycoproteins located at the cell surface.
• Form different types of complexes and junctions.
  • Join cells to cells.
  • Join cells to the extracellular matrix (ECM).
  • Join ECM to the cell cytoskeleton.

What Do They Do?

• Aid in:
  • Adhesion of cells to each other to form tissue.
  • Transmission of signals from outside the cell to inside the cell.
  • Migration of cells.

CAMs - Four Main Families

1. Cell-cell junctions (mainly Cadherins):

   • Cadherins rely on Calcium ions to function (Ca-adhesion!).
   • Transmembrane glycoproteins.
   • Link cytoskeleton of one cell to the cytoskeleton of another.

2. Cell-matrix junctions (large family of CAMs called integrins):

   • Integrins are found in focal adhesion and hemidesmosome type junctions.
   • Transmembrane proteoglycans – adhesion to extracellular matrix linkage to cytoskeleton.

3. Immunoglobulin superfamily

4. Selectins:

   • Special CAMs that bind cell-surface CHO.
   • Involved in inflammatory response.

Cell Adhesion in Animal Cells

• Joins involve interactions between transmembrane proteins in neighboring cells.
• The transmembrane proteins may be anchored inside the cell and associated with the cytoskeleton.
• The extracellular matrix is commonly linked to the underlying cells by plasma membrane proteins called integrins.

Intercellular Junctions Classification

• Occluding/organising Junctions
  • Tight junctions
• Adhering/anchoring Junctions
  • Actin filament attachment sites
    • Cell-cell junctions (adherens junctions)
    • Cell-Matrix junctions (focal adhesions)
  • Intermediate filament attachment sites
    • Cell-cell junctions – Desmosomes
    • Cell-matrix junctions – Hemidesmosomes
• Communicating junctions
  • Gap junctions
  • Chemical synapses

Tight Junctions

• Multiple strands of protein form the tight junction.
• More strands = more impermeability.
• Each strand formed from proteins:
  • Claudins
  • Occludins
  • ZO Proteins
• Tight Junctions as barriers to solute diffusion.
• Electron-dense tracer is added in the apical and basal sides of the cells.

Anchoring Junctions

• Connecting cytoskeleton
  1. Adherens junctions (cell-cell)
  2. Desmosomes (cell-cell)
  3. Focal adhesions and hemidesmosomes (cell-ECM)

Adherens Junctions

• They are composed of…
  • Cadherins – bind to the catenins that are connected to the actin filaments

Function

• Provide strong mechanical attachments between adjacent cells.
• They serve as a bridge connecting the actin cytoskeleton of neighboring cells through direct interaction.
• Cadherins mediate cell-cell adhesion
• Cadherins are linked to F-Actin via a diverse set of adaptor proteins
• Cadherins form Ca^{2+}-depended homophilic interaction (Ca-adhering)

Desmosomes

• Also called “Anchoring Junctions”
• Arranged randomly on the lateral side of cells membranes
• The adhesion protein bridges the space between the cells
• Desmosomes provide mechanically strong connections between epithelial cells.
• Plaque on the cytoplasmic side of the plasma membrane is attached to transmembrane adhesion proteins and to intermediate filaments (keratin fibres) that span the cell.

Function of desmosomes

• Fasten cells together into strong sheets
• Attach muscle cells to each other in a muscle
• Muscle tears can involve rupture of desmosomes
• Desmosomes contain specialized cadherin molecules and interact with intermediate filaments
• The autoimmune disease pemphigus vulgaris disrupts adhesion of epithelial cells mediated by desmosomes.
• Caused by auto antibodies against desmoglein
• Patients suffer from severe blister formation

Focal Adhesion

• Focal adhesions are contact points for the cell with the extracellular matrix.
• These complex structures regulate communication with the surrounding extracellular environment, signalling regulates diverse cellular processes.
• The principal components are integrins, which are αβ heterodimers that regulate cell–matrix and cell–cell interactions.

HemiDesmosomes

• Similar in form to Desmosomes.
• Desmosomes link two cells together
• Hemidesmosomes attach one cell to the extracellular matrix and therefore use a different adhesion protein.

Gap Junctions

• Connexons: assembly of six proteins that create gap between two plasma membranes
  • 6 connexin transmembrane proteins form a connexon hemichannel
  • Hemichannels of two adjacent cells form a gap junction with a central pore of 14Å
• Gap junctions allow passive transport (diffusion) of small molecules and ions

Functions:

• Rapid communication between neighboring cells, e.g. cardiomyocytes need synchronized actions
• Communication beyond nerve system, e.g. hepatocytes beyond sympathetic nerves need to be informed to produce glucose from glycogen
• Embryogenesis, form specific tissue with coupled group of cells

Summary of Cell Junctions

The Cytoskeleton

• Operational definition: Intracellular network of protein filaments insoluble in non-ionic detergents.
• Comments:
  • The cytoskeleton gives the cell strength, rigidity and shape; and is also responsible for cell motility and intracellular movements.

Cytoskeleton Functions

• Cells have specific shapes and internal organisation and carry out co-ordinated and directed movements.
• All of these properties are controlled by cytoskeleton – which is in effect the cellular cytomusculature.
• It is a characteristic feature of all eukaryote cells and was probably crucial to evolution of large complex single and multicellular organisms.

Components of the cytoskeleton

• In the cytosol, arrays of protein filaments form networks that give the cell its shape and provide a basis for its movements.
• Three main kinds of cytoskeletal filaments are
  1. microtubules (25-nm diameter) - Intracellular Traffic
  2. actin filaments (8-nm diameter) - Cell shape and locomotion
  3. intermediate filaments (10-nm diameter) - Mechanical strength

1. Microtubules

• These are hollow tubules ca. 25nm in diameter composed of a globular protein called tubulin.
• It is heterodimer composed of two closely related globular polypeptides: α & β tubulin that polymersise to form a tubule up to several microns in length.
• At least 20% of vertebrate brain is composed of tubulin!

Microtubules are dynamic structures

• Microtubules are polar – with plus (fast growing) and minus (slow growing) ends.
• The half-life of a microtubule is ~10 minutes.
• Dynamic instability – continues unless the + end is stabilised by attaching to molecule or cell structure. i.e attach a cap protein

Summary of microtubule structure

• Grow from
  • central structure – centrosome or other microtubule organising centre: the spindle pole or basal body
• Generates system of tracks where…
  • Organelles, vesicles and other cell components anchored
  • Guides intracellular transport of these and cytosolic macromolecules
• Make beating structures – cilia and flagella

Inhibitors of Microtubules

• Because of their dynamic nature microtubules are susceptible to drug action.
• Colchicine (used to treat gout since Egyptian times). This binds to tubulin subunits and prevents polymerisation. Used to inhibit spindle formation & arrest mitosis.
• Taxol – binds to tubulin subunits and prevents disaggregation. Used as a treatment for breast cancer.

Microtubules and their associated motor proteins

• Dyneins: Dumbell like globular molecules which move to negative end of microtubules towards centrosome
• Involved in organelle transport and mitosis. Ciliary dynein is motor protein responsible for bending.

Microtubules and Motor proteins

• Kinesins – Double stranded proteins composed with helical coil and small globular heads. Move towards the positive end of the microtubules away from centromere.
• Involved in meiosis, movement of synaptic vesicles along nerve axons.
• Cargo molecules are shuttled along microtubules to destinations.

Motor protein function

• Hydrolysis of ATP – gives energy for a cycle of conformational change of the head domain
• Release – movement - and binding of head
• ATP-dependent “walking” along microtubule
• Cycling through 3 conformations
  • ATP binding
  • ADP + Pi
  • ADP release

Microtubules and movement of cilia/ flagella

• Cilia – small hair-like projections of apical cell membrane
• Consists of a bundle of stable microtubules that grow from a basal body
• Role is to move fluid over cell surface
  • Respiratory tract epithelium – to move dust and dead cells up to throat in mucus from lungs/ bronchi
  • Oviducts - to move eggs along oviducts to uterus
  • Midline of embryo - to establish left-right axis

Beating of cilium - two different strokes

• Power stroke:
  • Fully extended stroke to move maximum amount o fluid
• Recovery stroke
  • curls back into position with minimal disturbance
• Difference in strokes ensures one direction to movement

Microtubular organisation in cilia and flagella

• Different organisation to the microtubule tracks
• Arranged as microtubule doublets arranged in a ring in around two single microtubules in a 9 + 2 pattern
• Additional proteins associated that project at regular intervals:
  • Cross linking protein nexin holds microtubules together
  • Motor protein to generate force – 2 rows of ciliary dynein