Cell and Molecular Biology

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Cell and Molecular Biology

• MSc Medical Microbiology 2004
• Lecture 1 The dynamic cell

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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
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Structure is governed by function
Secretion granules in the pancreas contain
digestive enzymes which will be discharged into
the intestine and insulin secreting cells with
much smaller granules

• Smooth endoplasmic reticulum in liver cells
  contains the protective drug metabolising enzymes

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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.

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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.

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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

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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

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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

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Microtubules radiate from a microtubule
organising centre
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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

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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

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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
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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
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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
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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.

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Motile Cells
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

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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

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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.
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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.
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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
  MWlt200

Hemidesmosomes and adhesion plaques attach the
cell to the basal lamina (basement membrane)