Cell Adhesion and Communication Flashcards

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1
Q

what is epithelial tissue?

A

covers the surface of internal and external organs

- layers of cells on top of a basement membrane

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2
Q

how do layers of epithelial interact?

A

the cells adhere laterally and to the basement membrane via cell matrix interactions

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3
Q

how can connections between cells be established?

A
tight junctions
adherens junctions
desmosomes
gap junctions
non-junctional adhesions
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4
Q

what is meant by tight?

A

impermeable to most molecules and is found in between epithelial cells

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5
Q

what is meant by attachment?

A

actin and intermediate filaments on adjacent cell, sticks cells to the ECM

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6
Q

what is mean by comminication?

A

connects the cytoplasm between adjacent cells

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7
Q

how can connections between cells and their underlying matrix be established?

A

hemidesmosomes

focal adhesions

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8
Q

what are the features of tight junctions?

A
  • bands of interconnected strands of integral membrane protein encircling the cell
  • as a complex they wrap around adjacent cells
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9
Q

what are sealing strands in tight junctions?

A
  • contain 3 transmembrnae proteins: claudins, occludins and JAMs.
  • proteins in the sealing strands attach to stably structural proteins
  • and transiently to signalling proteins
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10
Q

what proteins are the core of tight junction fibirls?

A

claudins

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11
Q

what do tight juncctions do?

A

form a tight barrier between epithelial cells

- not completely impermeable allows ions, solutes and some electrical currents

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12
Q

how do tight junctions differ?

A
  • different tight junctions allow different electric currents (vary in size and charge)
  • selectively from different claudins, how the different claudins arrange the loop
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13
Q

how do claudins interact with claudins from adjacent cell?

A

arrange to form a pore

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14
Q

what do occludins and JAMs do?

A

they stabilise (not structural)

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15
Q

where is an example of claudin specificity?

A

kidney (example):

  • Claudin 16  restricted to the ascending limb
  • Mg+ and Ca2+ not able to pass through the epithelial cells
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16
Q

what is paracellular transport?

A
  • Transport of substances across all epithelium by passing through the intracellular space between the cells
  • Regulated by claudins
  • Act as molecular sieves
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17
Q

what is transcellular transport?

A
  • Transfer by passing through cells cross both the apical and basolateral membranes
  • Allows the transport of substances against their concentration gradient
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18
Q

use glucose as an example of transcellular transport?

A
  • Example: absorption of glucose
     Across intestinal epithelium
     If we relied on diffusion it could only do this until equilibrium is reach
     ATPase and the GLUT2 in basolateral (not in the apical) ATP to sodium ions out of the cell = low concentration then Na+ flows into the cells and carries the glucose in
     Also important that the sodium/glucose symporter is in the apical not the basolateral
     Glucose flows down its concentration gradient into the bloodstream
     Only works if you have certain proteins on certain sides of the membrane
     Apical and basolateral membranes maintain unique identity.
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19
Q

what make up attachment junctions?

A

adherens junctions and desmosomes

- they are bridged by rod like structures

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20
Q

how to adherens junction connect to adjacent cells?

A
  • bridge to connect the actin cytoskeletons
  • link to actin filaments through catenins
  • the presence of cadherins that bind identical cadherins from neighbouring cells
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21
Q

what are cadherins?

A

transmembrane proteins

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22
Q

where do adherens junction have an important role?

A

in tissue organisation

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23
Q

what determines how tightly adherens junctions stick together?

A

the number and type of cadherins

24
Q

how to adherens junctions all link to the actin cytoskeleton?

A
  • regulate changes in cell shape in response to sheer stress

- zonular adhesions

25
Q

what are zonular adhesions?

A
  • cadherins - role in signalling - when disrupted they can enter the nucleus as a transcription factor
26
Q

what is the role of desmosomes?

A

add structural integrity, link intermediate filaments together through adaptor proteins

27
Q

what is the structure of desmosomes?

A

contains cadherins
as well as desmocollins and desmogleins (stabilising proteins)
can be called spot desmosomes as they stick together

28
Q

what is the function of desmosomes?

A
  • linked by stabilising proteins
  • linked to intermediate filaments through adaptor proteins
  • bridge the intracellular space and serve as docking sites for cystolic proteins
29
Q

what are hemidesmosomes?

A

form attachment junctions to connect cell to the underlying matrix

30
Q

where are hemidesmosomes?

A

located exclusively on the basal membrane

31
Q

what is the structure of hemidesmosomes?

A
  • have cytoplasmic plaques composed of integrin and that adaptor protein plectin
32
Q

what is the function of hemidesmosomes?

A
  • provide structural stability to the epithelial sheet

- anchor cells to basemembrane through cytoplasmic plaques that connect to intermediate filaments

33
Q

how do hemidesmosomes and desmisomes work together?

A

for structural integrity, allow intermediate filaments to form a network throughout the cell

34
Q

what are focal adhesions?

A

integrins link to the actin cytoskeleton to the babsement membrane

35
Q

what are integrins?

A

heterodimers of alpha and beta subunits
(18 alpha subunits and 8 beta subunits)
- 24 different integrin heterodimers known

36
Q

how do integrins associate?

A

non-covalently

37
Q

what do integrins bind to?

A

extracellular matric (ECM) components

38
Q

what is integrin specificity determined by?

A

composition of heterodimers

  • common beta subunit
  • variation in alpha subunit contributes to specificity
39
Q

what determines which ECM a cell can bind?

A
  • different integrins
  • different cell types express different integrins
  • different ECM have different composition
  • expression profile can change during development
40
Q

what can binding of integrins to ECM be altered by?

A

environment

41
Q

what do all known binding sites on ECM proteins contain?

A
  • an amino acid often aspartate

- many contain the sequence Arg-Gly-Asp

42
Q

what is inside out signalling?

A
  •  Activates talin and induces dimerization

 Talin binds to β integrin subunit causing a conformational change in the integrin extracellular domain  an example

43
Q

what is outside in signalling?

A

 Transduce information outside to inside
 When a cell binds to ECM it can cluster integrin’s forming a docking site for signalling molecules that then bring about changes inside the cell

44
Q

how can integrins regulate cell movement?

A
  • induce actin remodelling

- through intracellular trafficking

45
Q

how can integrins regulate cell movement through intracellular trafficking?

A
  • endocytosis of integrins can be used to break attachment of a substrate
  • allows a focal adhesion to move on
  • traffics into a compartment into an endosome
46
Q

what happens when trafficking is disrupted?

A
  • mistargeted to lysosome

- common in some cancers as you lose attachment

47
Q

where else are integrins importnat?

A

non-junctional cell adhesions

48
Q

what are gap junctions?

A
  • communication junctions
  • allows the direct transfer of ions/small molecules between adjacent cells
  • found in most vertebrae and invertebrae
  • only known means of cell to cell transport
  • also facilitates electrical signals between cells
49
Q

how can you spot a gap junction?

A

plasma membranes appear clustered together in the surround area with gaps bridge by channels projecting out of the plasma membrane

50
Q

what are connexions?

A
  • proteins in gap channel
51
Q

what is the structure of connexions?

A
  • have 4 transmembrane domains
  • 6 of these make up a conexxion
  • 2 connexons on adjacent cells form a channel
52
Q

what is the function of connexions?

A
  • transport small molecules - ions sugars amino acids nucleotides
  • electrically couples neighboring cells
  • have different permeability properties depending on connexions present
53
Q

what are the functions of gap junctions?

A
  • when you need rapid communication, eg reflex reactions
54
Q

what are mutations in gap junctions linked to?

A

heart disease

55
Q

how are gap junctions regulated?

A

alternate between open and closed states

  • large increases in intracellular calcium ion concentration and/or pH induce gap junction closure
  • gap junction closure prevents further damage to neighouring cells