KINE 1000 Lecture Notes - Lecture 13: Cytoskeleton, Phosphatidylinositol (3,4,5)-Trisphosphate, Filamin
4 Jun 2018
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Rac Activation and Actin Organization
• Rac activates actin accessory proteins
• Rac > ARP, filamin > actin webs forms
• Rac > decreases myosin activity> fewer stress fibers
• PI(,,)P does’t oe far fro GPCR > local foratio of acti etork ear
activated receptors
• Activation of GTPase Rac leads to alterations in actin accessory proteins that favor
foration of actin networks in lamellipodia. Ras activates WASp proteins family which
activates actin nucleation & branched web formation by ARP complex. Rac-GTP
activates protein kinase, PAK, which targets web-forming cross linker filamin and results
in decreases phosphorylation of myosin & leads to disassembly of myosin- less
contractile activity
Rho Activation & Actin Organization
• Rho activation > formins > more actin stress fibers
• Rho > more myosin activity, contraction
• Rho & Rac do opposite things
• GTPase Rho leads to nucleation of actin filaments by formins & increases contraction by
myosin. It promotes formation of contractile actin bundles like stress fibers. Activation
of myosin by Rho
External Signals can Dictate Direction of Cell Migration
• Chemotaxis is movement of cell towards/away from source of a diffusible chemical
• Cell of immune system (neutrophil) destroys pathogens
• External signals act through Rho family proteins to set a large scale polarity
• Chemotactic movement includes movement of while blood cells called neutrophils
towards source of bacterial infections.
- Receptors on surface of neutrophils enables them to detect low concentration of
bacterial proteins.
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Document Summary
Ras activates wasp proteins family which activates actin nucleation & branched web formation by arp complex. Rac-gtp activates protein kinase, pak, which targets web-forming cross linker filamin and results in decreases phosphorylation of myosin & leads to disassembly of myosin- less contractile activity. It promotes formation of contractile actin bundles like stress fibers. Receptors on surface of neutrophils enables them to detect low concentration of bacterial proteins. Neutrophils are guided towards bacterial targets b/c able to detect a difference in. 1% of diffusible peptides: chemotaxis of dictyostelium amoebae moves towards source of camp. Binding of chemoattractant to gpcr activates pi3ks , which activates rac gtpase. Accumulation of polarized actin web at leading edge causes further local enhancement of pi3k activity in postive feedback loop, strengthening induction of protrusion. At same time, binding of chemoattractant ligan to receptor activates another signalling pathway that turns on rho & enhances myosin contraction. Two process of rac & rho directly inhibit each other.
