Cell and Molecular Biology

Cell and Molecular Biology
MSc Medical Microbiology 2004
Lecture 1 The dynamic cell
The Structure of Cells
The interior of eukaryotic cells consists of organised structures (nucleus, mitochondria, lysosomes peroxisomes and,in some cells secretion granules) and of systems of membranes (the endoplasmic reticulum, the Golgi apparatus, the endosome system and a variety of transport vesicles) suspended in
a fluid (the cytosol) and contained within the plasma membrane
Structure is governed by function
Smooth endoplasmic reticulum in liver cells contains the protective drug metabolising enzymes
Secretion granules in the pancreas contain digestive enzymes which will be discharged into the intestine and insulin secreting cells with much smaller granules
All is not as it seems
Electron micrographs such as the ones on the last slide give the impression of a very static cell interior. This is not the case. The interior of the cell is rapidly changing with organelles and membrane systems breaking and rejoining. Furthermore there is active transport of proteins between organelles, for example proteins which will be secreted from the cell pass from one compartment to another.
Moving and touching cells
During embryonic life cells may migrate considerable distances from the site of differentiation to their final destination This migration may be observed in wound healing or in white blood cells hunting down bacteria.
The interior of a cell is thus a complex and dynamic structure and the effects of xenobiotics (chemicals not normally present in the body) will be equally complex even before we consider inter-actions between different cells and tissues.
Just Looking
For an example look at the intestinal epithelium We notice the beautiful alignment of the nuclei and the goblet cell granules. The apparent disorganisation of the subepithelium is only apparent
Elements of the Cytoskeleton
Three major types of filaments have been identified in eucaryotic cells
1) Microfilaments which are formed by polymerisation of actin molecules. These break down and reform rapidly
2) Microtubules which are formed by the polymerisation of tubulins and also breakdown and reform readily
3) Intermediate filaments formed by polymerisation of proteins such as keratin. These were thought to be very stable but it is now known that this is not always the case
Microtubules
1) Organise the endoplasmic reticulum and the Golgi apparatus
2) Act as a “railroad” connecting the trans golgi network to the cell surface and the early endosome compartments to the late ones
3) Form the spindle apparatus in mitotic cells
4) Act as motile elements in cilia and flagella
Microtubules radiate from a microtubule organising centre
Continued
To Summarise
Microtubules radiate from the microtubule organising centre
Vesicles may move along the microtubules in both directions – they act like an intracellular railroad
The rough endoplasmic reticulum is spread out by the microtubules like an umbrella on its spokes
Microtubules can interact with other cytoskeletal elements
Microfilaments
1) Form the “cortical cytoskeleton” which lies under, and is attached to the plasma membrane and is involved in control of cell shape
2) Assist in forming the terminal web and the microvilli of epithelial cells
3) Cause movement of cells
4) Form bundles which form the contractile elements skeletal, cardiac and smooth muscle cells
Organisation of actin
Actin microfilaments are normally found as bundles. These may be networks as in the cortical cytoskeleton and in smooth muscles cells, tight, highly parallel bundles as in filopodia, microvilli and skeletal muscle or as looser bundles as in stress fibres
Actin controls cell shape
The cortical cytoskeleton (actin plus associated proteins) not only determines the cell shape in fixed cells but also changes on shape as is the case with the platelet shown above
Actin microfilaments co-ooperate with other cytoskeletal elements
Actin microfilaments interact with other cytoskeletal elements . The picture shows the actin microfilaments that form the core of the microvillus interacting with intermediate filaments of the terminal web. Replacement proteins for the tip of the microvillus are transported along microtubules to the terminal web where they are transferred to microfilaments
Actin polymerisation
Actin microfilaments, like microtubules can rapidly polymerise and depolymerise. This is the major mechanism for cell motility. A very clear demonstration of how movement is possible is the movement of the intracellular bacterium listeria monocytogenes.
Motile Cells
While most cells in the body are fixed in place by attachments to each other and basement membranes, some, like neutrophils and macrophages remain motile. Free living single cells are generally motile and cell movement plays an important in early embryogenesis.
Microfilaments and microtubules interact to control cell movement. This will be considered in more detail in later lectures
Motile Cells
Intermediate Filaments
1) Form cables which stretch across the cell from desmosomes on one side to desmosomes on the other so giving strength to the cells
2) Hold the nucleus in place
3) May play a role in organising “permanent” cell extensions such as nerve axons
4) The nuclear lamina is formed by proteins called lamins whichare closelyrelated to intermediate filament proteins
Continued
Intermediate filamentsts are concentrated in the region round the nycleus and are responsible for holding the nucleus in place. Other imtermediate filaments raddiate to the cell surface and attach to desmosomes and hemidesmosomes giving strength to the cell.
Reinforced tissue
This micrograph shoes the distribution of the cytokeratin filaments (green) of cultured epithelial cells as compared with the plasma membrane (blue). Desmosome bind both stains and appear pale blue.
Connections
Cells in a tissue are bound to each other and to the extracellular matris both by single cell adhesion molecules and by junctional complexes. These are
Tight junctions which prevent proteins from passing across an epithelium
Adherens junctions which are anchoring points for microfilaments
Desmosomes which are anchoring points fpr intermediate filaments
Gap junctions provide cell-cell communication as they allow through ions and molecules with a MW<200
Hemidesmosomes and adhesion plaques attach the cell to the basal lamina (basement membrane)