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Cell Motility Q1 based on gambar kat FB group. The rest Dr.

Lau kata you guys should know

1. Cell movement is important for many body processes which included immune response, tissue repair, embryological development and disease aetiology. a. Describe the model of raking mechanism of chemotaxis over a substratum. Description The raking mechanism is one model proposed to account for the retrograde movement of large membrane constituents Large membrane constituents are bound to transmembrane adhesion molecules Transmembrane adhesion molecules are bound to the backward moving F-actin microfilaments Since the adhesion molecules on the substratum are fixed in place as the F-actin moves backwards, the lamellipodium (and cell) moves forwards

This mechanism proposed that the actin proteins are transported along cytoskeletal microtubules from the ER, forwards to the leading edge, where it becomes polymerized into the growing actin filament This is enhanced by the entry of Ca2+ at the leading edge Entry of Ca2+ is due to ligand gated Ca2+ channels which also respond to the chemo-attractant

General outline; Theres a sort of F-actin microfilaments treadmill that moves the cell forward As the cell moves forward, cellular component move and at the trailing edge a thin retraction fibre remains Detachment of this retraction fibre from the adhesion molecule of the substratum (probably by protease activity) allows the retraction fibre to be drawn back into the cell The large membrane constituents are recycled into vesicles, which fuse with the leading edge thus restoring the lipids and macromolecules to the leading edge

b. State the main groups of primary chemotactic ligands, its specific cell targets and effects Chemotactic ligands definition: the number of ligand molecules capable of causing chemotactic responses Classified as either primary or secondary chemotactic molecules

i Formyl peptides Specific cell target: not stated in lecture Effect: Affect inflammation and chemo-attractant effect on neutrophils granulocytes and monocytes

ii Complement 3a and complement 5a Specific cell target: Neutrophil granulocytes and monocytes Effects: intermediate products of the complement cascade

iii Chemokines Specific cell target: monocytes (by CC chemokines), neutrophils & granulocytes specific (by CXC chemokines) Effects: not stated in lecture

iv Leukotrienes Specific cell target: not stated in lecture Effects: elicits adhesion, chemotaxis and aggreagation of leukocytes

2. Three Principles of cell movement i Random motion in which cells are either not responding to any cues and simply moving in a random pattern ii Chemokines in which cells are moving in response to a chemical signal, but not moving directionally iii Chemotaxis in which the cells are moving purposefully in one direction towards (or away from) a chemical signal

3. Movement over substratum General outline; Cell attaches to the substratum via adhesion plaques Lamellipodia extend from the leading edge of the cell in the direction of movement Finger-like projection of plasma membrane and cytoplasm

There is a backward (retrograde) movement of the larger cell and membrane constituents away from the leading edge Upper surface of the cell becomes ruffled in appearance due to rapid F-actin polymerization Lamellipodium bind to focal adhesion sites on the substratum

Lamellipodium attaches to the substratum via new adhesion plaques Cellular materials are withdrawn from the tail along actin microfilaments (retraction fibre) The tail detaches and the remaining contents are drawn forward into the cell

Additional information from slides (can be important) Movement is initiated by ligand stimulation of a cell surface receptor The receptor is either; Long-term resident of the plasma membrane Induced and placed in the membrane to increase in number upon receipt of another signal E.g 7-TMS GPCR

When the ligand binds and induces the LICC, it is thought that the cell generates an internal gradient of PIP3 Responsible for the polymerisation of actin into fibres

As the concentration of the ligand and the PIP3 gradient in the cell increases, the rate of actin polymerisation increases

4. Clinical importance of cell motility Migratory potential of cells has relatively high importance in the development of several clinical symptoms and syndromes Altered chemotactic activity represents a significant clinical target Understanding cause and effect of these movements is important to design novel treatments to counter spread and infectivity Chemotaxis, either normal but inappropriately signalled or abnormal is of prime importance in the aetiology of the disease In atherosclerosis, the chemotaxis of monocytes towards the damaged lining of a blood vessel is normal but leads to the disease progression During embryological development cells of the yolk sac mus migrate to form mesechymal layers and primordial germ cells

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