Cell Adhesion and Communication Flashcards
what is epithelial tissue?
covers the surface of internal and external organs
- layers of cells on top of a basement membrane
how do layers of epithelial interact?
the cells adhere laterally and to the basement membrane via cell matrix interactions
how can connections between cells be established?
tight junctions adherens junctions desmosomes gap junctions non-junctional adhesions
what is meant by tight?
impermeable to most molecules and is found in between epithelial cells
what is meant by attachment?
actin and intermediate filaments on adjacent cell, sticks cells to the ECM
what is mean by comminication?
connects the cytoplasm between adjacent cells
how can connections between cells and their underlying matrix be established?
hemidesmosomes
focal adhesions
what are the features of tight junctions?
- bands of interconnected strands of integral membrane protein encircling the cell
- as a complex they wrap around adjacent cells
what are sealing strands in tight junctions?
- contain 3 transmembrnae proteins: claudins, occludins and JAMs.
- proteins in the sealing strands attach to stably structural proteins
- and transiently to signalling proteins
what proteins are the core of tight junction fibirls?
claudins
what do tight juncctions do?
form a tight barrier between epithelial cells
- not completely impermeable allows ions, solutes and some electrical currents
how do tight junctions differ?
- different tight junctions allow different electric currents (vary in size and charge)
- selectively from different claudins, how the different claudins arrange the loop
how do claudins interact with claudins from adjacent cell?
arrange to form a pore
what do occludins and JAMs do?
they stabilise (not structural)
where is an example of claudin specificity?
kidney (example):
- Claudin 16 restricted to the ascending limb
- Mg+ and Ca2+ not able to pass through the epithelial cells
what is paracellular transport?
- Transport of substances across all epithelium by passing through the intracellular space between the cells
- Regulated by claudins
- Act as molecular sieves
what is transcellular transport?
- Transfer by passing through cells cross both the apical and basolateral membranes
- Allows the transport of substances against their concentration gradient
use glucose as an example of transcellular transport?
- 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.
what make up attachment junctions?
adherens junctions and desmosomes
- they are bridged by rod like structures
how to adherens junction connect to adjacent cells?
- bridge to connect the actin cytoskeletons
- link to actin filaments through catenins
- the presence of cadherins that bind identical cadherins from neighbouring cells
what are cadherins?
transmembrane proteins
where do adherens junction have an important role?
in tissue organisation
what determines how tightly adherens junctions stick together?
the number and type of cadherins
how to adherens junctions all link to the actin cytoskeleton?
- regulate changes in cell shape in response to sheer stress
- zonular adhesions
what are zonular adhesions?
- cadherins - role in signalling - when disrupted they can enter the nucleus as a transcription factor
what is the role of desmosomes?
add structural integrity, link intermediate filaments together through adaptor proteins
what is the structure of desmosomes?
contains cadherins
as well as desmocollins and desmogleins (stabilising proteins)
can be called spot desmosomes as they stick together
what is the function of desmosomes?
- linked by stabilising proteins
- linked to intermediate filaments through adaptor proteins
- bridge the intracellular space and serve as docking sites for cystolic proteins
what are hemidesmosomes?
form attachment junctions to connect cell to the underlying matrix
where are hemidesmosomes?
located exclusively on the basal membrane
what is the structure of hemidesmosomes?
- have cytoplasmic plaques composed of integrin and that adaptor protein plectin
what is the function of hemidesmosomes?
- provide structural stability to the epithelial sheet
- anchor cells to basemembrane through cytoplasmic plaques that connect to intermediate filaments
how do hemidesmosomes and desmisomes work together?
for structural integrity, allow intermediate filaments to form a network throughout the cell
what are focal adhesions?
integrins link to the actin cytoskeleton to the babsement membrane
what are integrins?
heterodimers of alpha and beta subunits
(18 alpha subunits and 8 beta subunits)
- 24 different integrin heterodimers known
how do integrins associate?
non-covalently
what do integrins bind to?
extracellular matric (ECM) components
what is integrin specificity determined by?
composition of heterodimers
- common beta subunit
- variation in alpha subunit contributes to specificity
what determines which ECM a cell can bind?
- different integrins
- different cell types express different integrins
- different ECM have different composition
- expression profile can change during development
what can binding of integrins to ECM be altered by?
environment
what do all known binding sites on ECM proteins contain?
- an amino acid often aspartate
- many contain the sequence Arg-Gly-Asp
what is inside out signalling?
- Activates talin and induces dimerization
Talin binds to β integrin subunit causing a conformational change in the integrin extracellular domain an example
what is outside in signalling?
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
how can integrins regulate cell movement?
- induce actin remodelling
- through intracellular trafficking
how can integrins regulate cell movement through intracellular trafficking?
- 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
what happens when trafficking is disrupted?
- mistargeted to lysosome
- common in some cancers as you lose attachment
where else are integrins importnat?
non-junctional cell adhesions
what are gap junctions?
- 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
how can you spot a gap junction?
plasma membranes appear clustered together in the surround area with gaps bridge by channels projecting out of the plasma membrane
what are connexions?
- proteins in gap channel
what is the structure of connexions?
- have 4 transmembrane domains
- 6 of these make up a conexxion
- 2 connexons on adjacent cells form a channel
what is the function of connexions?
- transport small molecules - ions sugars amino acids nucleotides
- electrically couples neighboring cells
- have different permeability properties depending on connexions present
what are the functions of gap junctions?
- when you need rapid communication, eg reflex reactions
what are mutations in gap junctions linked to?
heart disease
how are gap junctions regulated?
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
