Lecture 18 (1): Focal Adhesions

Adhesion Proteins Conformations

• open/active

• closed/inactive

Integrins

• Transmembrane heterodimers

• Exist in two conformations:

  • Closed (inactive)

  • Open (active)

• Activate via

  • Inside-out signaling (talin binding)

  • Outside-in signaling (ECM ligand binding)

Focal Adhesion

• respond to mechanical stress and cluster

• main components:

  • talin

  • vinculin

• short lived and dynamic

• between migrating cells and ECM

Talin

• main component of focal adhesions

• dimer that binds integrin and actin

  • has active and inactive conformations

• talin buffers force through the folding and unfolding of its various rod domains

• brings FAK to the focal adhesions

Vinculin

• stabilizes talin and integrin at the focal adhesion

• opens up and aids integrin clustering for focal adhesion growth

• open and closed conformations

FAK

• focal adhesion kinases

• Activated at focal adhesions

Protein Domain

• region of a protein’s polypeptide chain that is self-stabilizing and that folds independently from the rest

• each domain forms a compact folded 3D structure

Myotendinous Junctions

• muscle attachement sites

• between tendons and muscles

• strong and permanent