Molecular Axon Guidance

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Presentation transcript:

Molecular Axon Guidance PC12 cell…. then NGF added NGF is neurotropic and neurotrophic

Guidance Factors Growth Factors

Netrin..was one of the first neurotropic factors

Findings

Netrin from FP

Netrin from FP, But perpendicular

Netrin in media

Cell locomotion like GCs Cell moves forward by extending filipodia & lamellipodia Focal adhesions are formed Cell is pulled forward

Diffusible Contact dependent

Extracellular matrix

Extracellular matrix Proteins of ECM - collagen

Extracellular matrix Proteins of ECM - proteoglycans

Proteins of ECM - fibronectin Extracellular matrix Proteins of ECM - fibronectin

Proteins of ECM - laminin Extracellular matrix collagen Proteins of ECM - laminin laminin

Interaction of cells with ECM INTEGRINS inactive

Interaction of cells with ECM INTEGRINS ligands have RGD motif differentiation motility growth survival functions of outside-in signals

Interaction of cells with ECM FOCAL ADHESIONS FA

Interaction of cells with ECM FOCAL ADHESIONS

CELL ADHESION MOLECULES Interaction of cells with cells CELL ADHESION MOLECULES

Interaction of cells with ECM and other cells CELL ADHESION MOLECULES VS ECM ATTACHMENT MOLECULES

Extracellular Ca 2+ Space Wnt E-Cadherin Frz II b-catenin p120 Dsh Frz II E-Cadherin p120 P b-catenin actin filaments a-catenin Gsk3b APC Axin P Tcf/Lef

Cadherins as Master Regulators of Morphology Focus is often on adhesive function: Cadherins as molecular glue Motility Passive Inhibition Rho-GTPases Active Promoter Adhesion AJ’s Type of Cadherin Stabilize others junctions Proliferation CDKI: p27/p21 Wnt Cadherins Receptor Signaling EGF FGF PDGF Transcriptional/ Nuclear Role -catenin/Wnt P120/kaiso In nucleus Actin Cytoskeleton -catenin Rho-GTPases Arp2/3

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