junctions, adhesion and ECM Flashcards
types of cell junctions found in epithelial cells
from apical to basal:
occluding junctions (tight junction)
anchoring junctions (adherens junctions, desmosomes)
channel forming junctions (gap junctions)
cell-matrix anchoring junctions (hemidesosome, actin-linked cell-matrix junction)
what is a junctional complex?
tight junction, adherens junction and desmosome
two classes of anchoring junctions
actin filament attachment sites: adherens (cell-cell) and actin-linked cell-matrix adhesions (cell-matrix)
intermediate filament attachment sites:
desmosomes (cell-cell) and hemidesmosomes (cell-matrix)
what is the channel-forming junction (ie. the equivalent of gap junctions) called in plants?
plasmodesmata
types of signal relaying junctions
chemical synapses (nervous system)
immunological synapses (immune system)
transmembrane ligand-receptor cell-cell signalling contacts - anchoring, occluding and channel-forming junctions can also have this function
what type of transmembrane adhesion protein is found in cell-cell junctions?
Cadherins
for adherens junctions and desmosomes
what type of transmembrane adhesion protein is found in cell-matrix junctions?
integrins
for actin-linked cell-matrix junctions and hemidesmosomes
what ion do cadherins proteins depend on?
Calcium ions
two classes of cadherins
classical (N-cadherin, E-cadherin)
non-classical (desmocollins, desmogleins)
structure of the extracellular region of classical cadherin
contains five copies of the extracellular cadherin domain separated by flexible hinge regions
Ca2+ ions bind at each hinge to prevent flexing (hence Ca2+ dependent)
how is adhesion generated at the extracellular region of classical cadherin?
the cadherin domain at the N-terminal tip of one molecule binds to the same at another molecule, effectively connecting two cadherins proteins
how does cadherin influence developing tissues?
changing patterns of cadherin expression during early development (embryo stage) guide the organisation of tissues (groups of cells segregate from one another according to the cadherins they express)
define mechanotransduction
any mechanism by which cells convert mechanical stimuli into biochemical activity
how does mechanotransduction happen in an adherens junction?
increased tension sensed
respond by strengthening actin linkages
(actin filaments within cell pulled by non-muscle myosin II –> unfolds domain in ⍺-catenin, exposing binding site for adaptor protein vinculin, which promotes additional actin recruitment)
main function of desmosomes
give epithelia mechanical strength
structural components of desmosomes
dense layer of plaque on cytoplasmic side of PM connected to intermediate filaments
transmembrane non-classical cadherins (desmoglein/desmocollin) bind to plaques and interact in extracellular domains to hold adjacent membranes together
structure of hemidesmosomes
very similar to desmosomes but transmembrane adhesion protein is integrin rather than cadherin
binds to basal lamina
transmembrane proteins in tight junctions
claudin and occludin proteins
role of tight junctions in transcellular transport (of glucose)
transcellular = movement across membranes
tight junctions confine transport proteins to different regions of the PM and block back flow –> one-way transfer of nutrients
eg. active transporters for glucose at apical surface, passive transporters at basolateral membrane
main function of gap junctions
couples cells both electrically and metabolically through the creation of direct channels between cytoplasms of adjacent cells
what molecules can pass through a gap junction and why?
pore ~1.5nm diameter
only allows the exchange of INORGANIC IONS and some SMALL WATER-SOLUBLE MOLECULES (sugars, amino acids, nucleotides, vitamins, signalling molecules)
but not macromolecules like proteins / nucleic acid
types of cell-cell adhesion molecules
cadherins (classical and desmosomal)
Ig family members
Selectins (blood/endothelial cells only)
Integrins (on blood cells)
what type of cell-cell adhesion molecule does not depend on calcium?
members of the immunoglobulin superfamily (Igs)
where are Ig cell-cell adhesion molecules found? give examples
ICAM (Intercellular cell adhesion molecules) - expressed on endothelial cell surfaces and bind (heterophilically) to integrins on white blood cells
also at immune synapse - aids in binding antigen presenting cell to (integrin-presenting) T-cell
NCAM (neural “””) - found on neurons and other cell types (homophilic binding)
VCAM (vascular) also recognises white blood cell integrins
two major activity states of integrins
inactive (folded)
active (extended, with strong ligand binding)
what is the extracellular matrix made up of?
ECM made up of glycosaminoglycan chains that occupy large amounts of space in the form of hydrated gels
and proteins (fibrous=collagenu and non collagen glycoproteins)
proteoglycans
GAG chains covalently linked to a core protein
(collagen is a major protein in the ECM)
how is the ECM produced?
secreted by cells
fibroblasts produce a large portion of connective tissue
what is the basal lamina?
a special form of the ECM - a thin layer that lies beneath epithelial cells
three ways the basal lamina is organised
- surrounding cells (like muscle cells)
- lie underneath sheets of epithelial cells
- separating two sheets of cells (eg. epithelial / endothelial cells in the kidney glomerulus)
what are features of GAGs?
highly charged –> stiff and highly hydrated
multiple units of sugar (repeating disaccharide sequence)
describe the structure of fibrous collagen
long stiff triple-stranded helical structure of collagen polypeptide 𝛂chains
with intra and intermolecular crosslinks within/between chains due to modified side chains (lysine –> hydroxylysine)
describe the structure and function of fibronectin
a large glycoprotein dimer that helps organise the ECM
has multiple domains with specific binding sites for other matrix macromolecules
binds to integrins via RGD motif
laminin
a multi-domain glycoprotein that binds to collagen, major component of the basal lamina and anchoring it to cells
