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39 Cards in this Set
- Front
- Back
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Describe growth cones?
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the sensory tip of a growing neurite that translates extracellular info to cellular response -cell surface receptor activation > Transcellular signals > impinge on skeletal machinery to change direction |
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Describe microtubules of growth cone?
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form backbone -rarely invade filopodia |
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Describe lamellipodium?
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veil-like cytoplasm extensions containing networks of actin -reorganised to stabilise MTs in orientation dictated by actin filaments |
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Describe filopodia?
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polarised F-actin
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Describe cytoskeleton dynamics of growth cone?
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ATP-actin added to barbed/distal end of actin filament -hydrolysed to ADP-Pi-actin -slow dissociation of Pi > ADP-actin which is released from proximal/pointed end -occurs at same rate (TREADMILLING) |
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Describe microtubule dynamics? |
alpha + beta tubulin repeating units -a-GTP-b-tubulin added to distal end and a-GDP-btubulin removed from proximal end -post-translational modifications ie acetylation to stabilise |
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How Is axon growth initiated?
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protrusion of filopodia + lamellipodia > ENGORGEMENT (influx of MT + organelles) |
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Describe actin binding proteins in the growth cone?
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ADF/cofillin - severing/recycling Ena/Vasp - barbed end anti-capping |
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Describe ADF/Cofillin recycling?
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family of disassembling proteins -severs filaments + dissociated ADP-actin -activated by phosphatases -inactivated by LIM kinase |
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Describe Rho-GTPases?
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family of G-proteins that mediate cytoskeletal dynamics -ie Rho, Rac, cdc42 |
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How is Rho GTPase activated and inactivated?
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activated by GEFs that phosphorylates Rho-GDP>Rho-GTP to activate enzymes inactivated by GAPs to dephosph + inactivated |
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Name positive effects of Rho-GTPases?
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cdc42 + Rac activate Scar + N-WASP > filament branching also block MLCK blocking myosin + promoting filopodial elongation |
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Describe negative effects of Rho GTPase?
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myosin promotes backward movement of actin preventing elongation Rho blocks MLC phosphatase stimulating myosin |
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Describe chemical guidance?
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chemoattraction ie NGF repulsion associated with growth cone collapse |
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Describe physical guidance?
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tram lines - piggy back along pre-existing axons continuous chain of cells - ie epithelium along segmental boundaries |
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Describe electrical guidance?
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neurites growth towards negative
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Describe Trk signalling?
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Trk = TK receptor that binds NGF -3 models (GINTY + SEGAL, 2002) |
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Describe models of Trk signalling? |
signalling endosome - lig-receptor internalised bt endocytosis + Retrograde transported to nucleus > neuronal survival domino model - ligand binding at axon terminal causes propagated Trk phosph back to nucleus retrograde effector: messenger molecules activates in distal axon + transported back to cell body to bind to Trk |
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Describe growth v retraction?
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balance between actin polymerisation + depolymerisation -promoting cues: ECM or CAMS promote F-actin assembly + block actin depolymerisation -inhibtion cues ie myosin |
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Describe cell adhesion molecules?
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Ig superfamily ie CAMs Cadherins - ca dependent CAMs |
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Describe Ig superfamily?
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support axon growth -characterised by Ig domains + fibronectin III repeats -bind integrins + other Ig CAMs |
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Describe cadherins?
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transmembrane proteins -support axon growth + involved in axon piggy backing -form adherin junctions |
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Describe netrins?
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4 receptors - DCC, UNC5, neogenin + A2BR -DCC: attractive + outgrowth to activate Rho GTPase, Rac + cdc42 -UNC5 with DCC coreceptor - repel -A2Br - netrin induced growth cone guidance |
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Describe ephrins?
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axon repulsion by binding to Eph receptors -group A secreted + receptors GPI anchored -group B membrane bound + Receptors transmembrane -expressed in gradeitnts in tectum + midline structures during development |
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Describe myelin proteins?
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Nogo, MAG + oMgP -bind to Nogo receptor with p75 coreceptor > Rho activation > growth cone collapse -thought to be main reason CNS axons don't degenerate |
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Give example of axon guidance?
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LEGG + OCONNOR, 2003 -grasshopper -mutated sema-2a = pathfinding errors |
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Describe PNI?
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wallerian degeneration -nerve distal to injury degenerates -schwann cells invade + divide -macrophages arrive + scavenge debris -schwann cells remain |
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Describe CNI?
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extremely slow + myelin components linger -inhib molecules upregulated at site of injury |
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Describe role of cAMP?
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HIGH cAMP> active Epac > chemoatttraction + axon growth as in embryo LOW cAMP> less Epac + PKA dominates > repulsion |
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Describe potential role of cAMP?
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connection between CNS that supports growth + one where no regeneration |
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Describe retinal projection pathway?
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RGCs go from retina to brain, most cross over at optic chiasm -in mammals, ventrolateral RGCs project ipsilaterally -in humans target is lateral geniculate nucleus but tectum in lower animals |
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Describe route of retinotectal pathway?
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retina ONH Optic nerve brain optic chiasm optic tract tectum |
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Describe retinotectal pathway in the retina?
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RGCs first neuroepithelial cell to differentiate -start in centre guided by inhibitory CSPG -later axons may piggy back along existing ones as all express CAM |
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Describe optic nerve head? |
once at ONH, netrin guides out of eye -netrin cant diffuse far so acts locally by activating cAMP in growth cone |
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Describe optic chiasm? |
once through ONH, retinal axons attraction for netrin switched off -ephrin b expressed at midline in animals with ipsilateral axons because these axons have receptros > deflection from midline -slits also at chiasm to confine to correct routes |
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Describe optic tract?
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fish + frog axons extend in optic tract close to surface of brain with 1st projecting axons lying deepest -if tract rotated, axons rotate too -later axons grow on pial surface of nerve pushing axons deeper but kept to superficial pathways by Tenascin-R |
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Describe tectum?
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retinal axons make characteristic posterior turn in dorsal diencephalon to grow into tectum -if FGF receptor mutated, this doesn't happen -disturbed heparin sulphate (ECM) also induces pathfinding errors |
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Describe axon positioning on tectum?
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grow preferentially on anterior tectum -inhibitory ephrins -eph receptors expressed by RGCs in gradients across tectum + retina -temporal retinal axons have more receptors so inhibited from projecting into deep tectum |
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Describe additional causes for anterior tectum preference?
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netrin in post tectum that repels
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