slide set 14 Flashcards
epithelial tissue vs. connective tissue
epithelial tissue: mechanical stresses are transmitted from cell to cell by cytoskeletal filaments anchored to cell-matrix and cell-cell adhesion sites
connective tissue: extracellular matrix directly bears mechanical stresses of tension and compression
type of cell-cell junctions
tight junction
adherens junction
desmosome
gap junction
tight junction
seals gap between epithelial cells
adherens junction
connects actin filament bundle in one cell with that in the next cell
desmosome
connects intermediate filaments in one cell to those in the next cell
gap junction
allows the passage of small water-soluble molecules from cell to cell
hemidesmosome
anchors intermediate filaments in a cell to extracellular matrix
tight junctions
made of 2 membrane proteins
claudins: essential for formation
occludins: limit permeability
extracellular domains of each bind tightly to each other
homophilic binding: the proteins bind “self”
tight junctions prevent…
small molecules from passing between cells
EX: epithelial cells of small intestine, skin, provide structure to epithelium
tight junctions and diffusion
tight junctions can limit membrane protein diffusion to zones within a cell’s plasma membrane
tight junctions confine transport proteins to diff regions of the plasma membrane in epithelial cells of the small intestine
gap junctions
pores between cells
allows small molecules to move from one cell to another
how to test if cells are connected by gap junctions
inject small dye into one cell
see if dye moves into adjacent cells
types of gap junctions
channels, connexons, connexins
2 connexons form a channel
how do cells assemble gap junctions?
- use a fluorescent tag that can be photoconverted from one fluorescent color to another
- convert the tag on older connexins to green, the remaining connexins are labeled with a red tag
- new connexons are added to the outside edges of a gap junction
assembling gap junctions
new connexons inserted into plasma membrane by exocytosis (like other integral membrane proteins) and then diffuse in the plane of the membrane until they bump into the periphery of a connexon plaque and are trapped
anchoring junctions
cells adhere to each other or adhere to the extracellular matrix through anchoring junctions
a cytoskeletal filament attaches to a transmembrane protein through adaptor proteins (cytoskeletal filament can be actin or intermediate filaments)
membrane protein for cell-cell contact is a cadherin protein
membrane protein for cell-ECM is an integrin protein
cadherin protein function
cell-cell contact
adherens junction
desmosome
integrin protein function
cell-ECM contact
actin-linked cell-matrix junction
hemidesmosome
cadherin protein family
share homology domains but also have differences among individuals
cytoplasmic tail varies among family members
extracellular cadherin domain is shared by all cadherins
(domains are fairly rigid, hinge regions in between domains are more flexible)
cadherin structure
EC region of classic cadherin has 5 copies of extracellular cadherin domain separated by flexible hinge regions
Ca2+ ions bind at each hinge to prevent it from flexing
EC region is rigid and curved
to form cell-cell adhesion, cadherin at N-terminal tip of one cadherin molec binds N-terminal domain from cadherin molec on a diff cell
how did we find out structure of cadherin
X-ray diffraction
role of calcium in cadherin
calcium prevents hinge region from flexing
when Ca2+ is bound, there is limited flexibility and EC domain extends away from cell membrane
when Ca2+ isn’t bound, hinge regions are flexible and floppy
cadherins are like velcro
each protein’s attachment to their partner is relatively weak, but many weak attachments in parallel are strong
homophilic binding
individual cells bind to cells expressing the same cadherin
homophilic binding experiment
- take cells that don’t express cadherins (L Cells)
- Transfect with a plasmid to express E-cadherin or N-cadherin and mix them together
The cells sort themselves into islands!
they sorted themselves by the type and level of cadherins they express
cadherin expression changes during development as tissues form
as patterns of gene expression change the different groups of cells segregate according to the cadherins they express
adherens junctions
cytoskeletal filament is actin
adaptor proteins are catenins, which bind to cytoplasmic tail of cadherin and link to actin and associated proteins (including myosin II)
mature adherens junction formation
100s - 1000s of cadherins
- membrane protrusions initiate cell-cell contact
- actin and cadherin recruitment expands junction (recruited by Rac)
- actin remodeling and myosin recruitment expands the adherens junction
tension
myosin II and attachments generate tension
2 cells pull equally on each other
cell-cell junctions can sense increased tension and respond by strengthening their actin linkages (tension sensing is done by alpha-catenin)
desmosomes
cadherins linked to intermediate filaments through adaptors
Pemphigus
autoimmune disease
patients make antibodies against their own cadherins that form desmosomes
causes severe blistering of skin
keratin intermediate filament networks of adjacent cells are indirectly connected to one another through desmosomes
and to basal lamina through hemidesmosomes
