slide set 15 Flashcards
integrins what are they and what do they bind
membrane protein that binds the basal lamina
integrins structure
dimer of alpha and beta subunits
24 types in human (8 beta, 18 alpha)
integrins bind extracellularly to ECM proteins and intracellularly to linker proteins that attach to actin
important linker protein
talin!
focal adhesions
clusters of multiple integrins bound to talin, linking to bundles of actin filaments (stress fibers)
assembly
assembly and disassembly must occur in the right space at the right time for motility
how do we study the role of focal adhesions in cell migration?
- fluorescently label a protein found in focal adhesions (EX: vinculin) and observe localization over time
- in video, cell moves with polarity
ECM aka
extracellular matrix
cells have to make and release attachments to ECM
- Outside-in signaling
- integrin attachment to ECM triggers actin attachment on the inside
- Inside-out signaling
- signals stimulate actin and associated proteins to associate with integrins
- this changes conformation of the extracellular domain to bind ligand
active vs inactive integrin
inactive (weak binding) state (folded)
active (strong binding state) (unfolded)
differences are due to changes in structure
used data from X-ray crystallography
many integrins cluster together to form….
strong focal adhesions!
many other proteins cluster on the cytosolic side
(some bind to integrin tail, actin, or other proteins)
some of the proteins that make up a focal adhesion are enzymes that can detect tension generated by attachment to the ECM (more tension stabilizes the complex and forms larger adhesions
FAK aka
focal adhesion kinase
when is FAK active
FAK is active when cells are attached
talin and mechanical sensing
talin contributes to mechanical sensing by integrin-based cell-matrix adhesions
tension causes talin to unfold partially and expose multiple sites to bind vinculin
vinculin binds actin filaments, which creates more tension and anchors for actin filaments
talin is a tension sensor
Extracellular matrix (ECM)
cells synthesize and secrete the ECM and then organize it into a larger structure
talin positive feedback loop
tension leads to binding leads to more tension