Membrane Proteins 2 Transport of large molecules

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Membrane Proteins 2
Transport of large molecules
Vesicular Transport
• Transport of large particles and
macromolecules across plasma membranes
– Exocytosis – moves substance from the cell
interior to the extracellular space
– Endocytosis – enables large particles and
macromolecules to enter the cell
– Phagocytosis – pseudopods engulf solids and bring
them into the cell’s interior
Vesicular Transport
Changes in cytoskeletal proteins is required to
support endo/exo/phagocytosis
Functions of the Cytoskeleton
• Support, structure, remodeling
Actin microfilaments - Anchoring
25nm
25nm
2 stranded helical polymers of actin
Flexible structures
Diameter 5-9nm
Concentrated beneath plasma membrane
Anchors cytoskeleton to protein of the cell membrane.
Interacts with other proteins, eg myosin
Intermediate filaments- Strength and stability
25nm
25nm
Ropelike fibres
Diameter 10nm
Includes meshwork ‘nuclear lamina’ beneath inner nuclear membrane
Fibres stretch across cytoplasm; stabilizes position of organelles
Provides mechanical strength,
Microtubules -Shape & movement
25nm
25nm
Long hollow cylinders, straight, attached at a centrosome
Diameter 25nm
Made of tubulin
Allows for shape change & movement of organelles within cell
Phagocytosis is dependent on actin polymerization
and myosin (Myo) contraction
MyoB is increased
at the phagocytic
cup
MyoK is also
increased
Schematic representation
of the phagocytic cup and
furrow
Actin-binding proteins are enriched in distinct territories in
the phagocytic furrow.
A MyoK layer is
surrounded by
a myosin II layer
A MyoK layer is
surrounded by a
plasma membrane
layer
Harnessing actin dynamics for clathrin-mediated
endocytosis
Marko Kaksonen, Christopher P. Toret & David G.
Drubin
Nature Reviews Molecular Cell Biology 7, 404-414
(June 2006)
In CNS: Microglia
Google: The process of phagocytosis (Youtube)
Endocytosis
Endocytosis of cholesterol molecule
Transport of iron into the cell
1. Holotransferrin (HOLO-TF) binds to the
transferrin receptor (TfR)
2. Complexes localize to clathrin-coated
pits.
3. Invagination occurs…endocytosis.
4. Endosomes form & are acidified
by a proton pump.
5. Acidic pH releases iron from
transferrin (Tf)
6. Apotransferrin (APO-TF)-TfR
complex is returned to membrane.
7. Dissociation occurs
8. Iron may be targeted to mitochondria.
NOTE: In non-erythroid cells, iron is stored
in the form of ferritin and haemosiderin
Clathrin-Mediated Endocytosis
Figure 3.13
Exocytosis
Figure 3.12a
Ion Channels
Ion Channels are the Second Major Class of Transport Proteins
Ion channels differ from carriers in always working in passive
transport, their exquisite selectivity, and their higher rate of
transport.
A single ion channel may transport up to 100 million ions per second, a
rate 100,000 times higher than the fastest carrier.
Ion channels are on all cells, but reach their highest level of
sophistication on electrically excitable cells like neurons.
Channel Opening and Closing is Regulated in Three Broad Ways
Receptors
SIGNALLING THROUGH
Ionotropic receptors
Metabotropic receptors
or G-protein-linked
Enzyme-linked receptors
(eg Tyrosine kinase-linked receptors)
Others to follow
Ionotrophic
Receptors
G-protein-linked receptors
G-protein-linked receptors
Tyrosine kinase receptors
Note steps involved:
1. Ligand Reception
2. Receptor Dimerization
3. Catalysis (Phosphorylization)
4. Subsequent Protein Activation
5. Further Transduction
6. Response
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