Molecular Axon Guidance

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PC12 cell….then NGF added

NGF is neurotropic and neurotrophic

Growth FactorsGuidance 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 & lamellipodiaFocal adhesions are formedCell is pulled forward

Diffusible Contact dependent

Extracellular matrix

Extracellular matrix

Proteins of ECM - collagen

Extracellular matrix

Proteins of ECM - proteoglycans

Extracellular matrix

Proteins of ECM -

fibronectin

Extracellular matrix

Proteins of ECM - laminin

collagen

laminin

Interaction of cells with ECM

inactive

INTEGRINS

Interaction of cells with ECM

INTEGRINS

functions of outside-in signals

differentiationmotilitygrowth survival

ligands have RGD

motif

Interaction of cells with ECM

FOCAL ADHESIONS

FA

Interaction of cells with ECM

FOCAL ADHESION

S

Interaction of cells with cells

CELL ADHESION MOLECULES

Interaction of cells with ECM and other

cells

CELL ADHESION MOLECULES VS

ECM ATTACHMENT MOLECULES

Tcf/Lef

PE-Cadherin

-catenin p120

P

Wnt

Dsh

Frz II

ExtracellularSpace

actinfilaments

-catenin

Ca 2+

Gsk3

APCAxin

• Focus is often on adhesive function: Cadherins as molecular glue

Cadherins as Master Regulators of Morphology

Cadherins

Actin Cytoskeleton

-cateninRho-GTPasesArp2/3

Proliferation

CDKI: p27/p21Wnt

Motility

Passive InhibitionRho-GTPasesActive Promoter

Adhesion

AJ’sType of CadherinStabilize others junctions

ReceptorSignaling

EGFFGFPDGF

Transcriptional/Nuclear Role

-catenin/WntP120/kaisoIn nucleus