slide set 15 Flashcards

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1
Q

integrins what are they and what do they bind

A

membrane protein that binds the basal lamina

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2
Q

integrins structure

A

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

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3
Q

important linker protein

A

talin!

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4
Q

focal adhesions

A

clusters of multiple integrins bound to talin, linking to bundles of actin filaments (stress fibers)

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5
Q

assembly

A

assembly and disassembly must occur in the right space at the right time for motility

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6
Q

how do we study the role of focal adhesions in cell migration?

A
  • fluorescently label a protein found in focal adhesions (EX: vinculin) and observe localization over time
  • in video, cell moves with polarity
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7
Q

ECM aka

A

extracellular matrix

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8
Q

cells have to make and release attachments to ECM

A
  • 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
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9
Q

active vs inactive integrin

A

inactive (weak binding) state (folded)

active (strong binding state) (unfolded)

differences are due to changes in structure

used data from X-ray crystallography

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10
Q

many integrins cluster together to form….

A

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

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11
Q

FAK aka

A

focal adhesion kinase

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12
Q

when is FAK active

A

FAK is active when cells are attached

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13
Q

talin and mechanical sensing

A

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

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14
Q

Extracellular matrix (ECM)

A

cells synthesize and secrete the ECM and then organize it into a larger structure

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15
Q

talin positive feedback loop

A

tension leads to binding leads to more tension

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16
Q

ECM includes….

A
  • bone, teeth
  • tendon
  • ligament
  • cornea
  • cartilage
  • basal lamina
  • connective tissues
  • the proteins that make up the ECM provide strength and support, but also function in cell signaling (chemical and mechanical)
17
Q

3 broad categories of ECM proteins

A

proteoglycans and GAGs

fibrous proteins

glycoproteins

18
Q

basal lamina

A

thin layer of ECM that separates epithelial cells from the connective tissue

prevents fibroblasts from migrating into epithelial tissue, but immune cells can cross

cells on both sides secrete the proteins that make up the basal lamina

multiple components of ECM proteins are assembled to form it

components vary but most include laminin, type IV collagen, and sometimes fibronectin

19
Q

glycoproteins

A

laminin is the primary organizer of the basal lamina

other examples: nidogen, fibronectin

laminin anchors proteins to cells

image is electron micrographs of laminin molecules shadowed with platinum

20
Q

structural model of basal lamina attached to a cell’s integrins

A
21
Q

other type of glycoproteins in ECM

A

fibronectin, CYR61, tenascin, thrombospondin (don’t memorize)

many are large scaffold protein with multiple copies of specific protein-interaction domains

22
Q

proteoglycans

A

hyaluronan, perlecan, decorin, aggrecan

a protein core that is covalently attached to a sugar (specifically a glycosaminoglycan [GAG])

sugars provide hydration to tissues

the sugars are negatively charged, which attracts positively charged water molecules to form a hydrated gel

GAG sugars are not branched (unlike previous sugars we discussed)

23
Q

fibrous proteins

A

EX: type IV collagen, fibrillar collagen

collagens are major proteins of ECM

formed of 3 polypeptide chains, each called an alpha chain

alpha chains wrap around each other to form a stiff triple-stranded helix

24
Q

collagen molecules associate together into….

A

fibrils and fibers

25
Q

how do cells organize collagens

A

cells pull on collagens and organize them

2 pieces of chick embryo heart were cultured on a collagen gel

individual fibroblast cells migrate on the collagen, pulling on in and shaping it into fibers between the 2 pieces in the process

26
Q

ECM degradation

A

cells must degrade the ECM

ECM need to be degraded for normal turnover of proteins, remodeling of the ECM and for cells to migrate past it

extracellular proteases degrade ECM