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HMB435 Lecture 1 Sept 9th.docx

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Human Biology
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Andras Kapus

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HMB435 Lecture 1 Sept 9 2013 MIGRATION - Migration: requires a machinery to convert chemical energy to kinetic energy - two types of migrations: mesenchymal and ameboid. - two types of ameboid migrations: one that needs actin to occur and one doesn’t (BLEBBING) - Ameboid migration doesn’t need a stable surface. Eg neutrophils move in ameboid fashion in blood - Mesenchymal migration requires integrins: connect the outside with the inside to provide connection with a stable surface for movement - BLEBBING; a new idea, not fully formed or accepted: DOES NOT NEED ACTIN. cell body attaches weakly to the surface and the cytoskeleton breaks to form a bubble, the insides fill/spill into the ‘new bubble’ eg. Tumour cells do this - Tumour cells can be both ameboid and mesenchymal - EXPERIMENT: actin’s function in migration was determined by inhibiting actin polymerization… when this was done, migration stopped - END: myosin contraction - FRONT: actin polymerization ACTIN - Actin is a slow enzyme: the barbed end (+) has a low Kd and is more energetically favourable side to add the monomers to add onto. - ATP is bound to the brabed end and is hydrolyzed to form ADP. Barbed end has a higher affinity for ATP. ATP is not required for polymerization - Actin works by treadmilling. It can be branched and cut. NUCLEATION: - Nucleation: bind atleast three monomers of actin together to start polymerization (linear) - Decapping enzymes: allow depolarization to occur -  these are not proteases, no covalent bonds are broken -  regulated by Rho proteins - EGF slide: cells treated w
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