junctions, adhesion and ECM

Question 1

types of cell junctions found in epithelial cells

Answer 1

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)

Question 2

what is a junctional complex?

Answer 2

tight junction, adherens junction and desmosome

Question 3

two classes of anchoring junctions

Answer 3

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)

Question 4

what is the channel-forming junction (ie. the equivalent of gap junctions) called in plants?

Answer 4

plasmodesmata

Question 5

types of signal relaying junctions

Answer 5

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

Question 6

what type of transmembrane adhesion protein is found in cell-cell junctions?

Answer 6

Cadherins

for adherens junctions and desmosomes

Question 7

what type of transmembrane adhesion protein is found in cell-matrix junctions?

Answer 7

integrins

for actin-linked cell-matrix junctions and hemidesmosomes

Question 8

what ion do cadherins proteins depend on?

Answer 8

Calcium ions

Question 9

two classes of cadherins

Answer 9

classical (N-cadherin, E-cadherin)
non-classical (desmocollins, desmogleins)

Question 10

structure of the extracellular region of classical cadherin

Answer 10

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)

Question 11

how is adhesion generated at the extracellular region of classical cadherin?

Answer 11

the cadherin domain at the N-terminal tip of one molecule binds to the same at another molecule, effectively connecting two cadherins proteins

Question 12

how does cadherin influence developing tissues?

Answer 12

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)

Question 13

define mechanotransduction

Answer 13

any mechanism by which cells convert mechanical stimuli into biochemical activity

Question 14

how does mechanotransduction happen in an adherens junction?

Answer 14

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)

Question 15

main function of desmosomes

Answer 15

give epithelia mechanical strength

Question 16

structural components of desmosomes

Answer 16

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

Question 17

structure of hemidesmosomes

Answer 17

very similar to desmosomes but transmembrane adhesion protein is integrin rather than cadherin
binds to basal lamina

Question 18

transmembrane proteins in tight junctions

Answer 18

claudin and occludin proteins

Question 19

role of tight junctions in transcellular transport (of glucose)

Answer 19

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

Question 20

main function of gap junctions

Answer 20

couples cells both electrically and metabolically through the creation of direct channels between cytoplasms of adjacent cells

Question 21

what molecules can pass through a gap junction and why?

Answer 21

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

Question 22

types of cell-cell adhesion molecules

Answer 22

cadherins (classical and desmosomal)
Ig family members
Selectins (blood/endothelial cells only)
Integrins (on blood cells)

Question 23

what type of cell-cell adhesion molecule does not depend on calcium?

Answer 23

members of the immunoglobulin superfamily (Igs)

Question 24

where are Ig cell-cell adhesion molecules found? give examples

Answer 24

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

Question 25

two major activity states of integrins

Answer 25

inactive (folded)

active (extended, with strong ligand binding)

Question 26

what is the extracellular matrix made up of?

Answer 26

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)

Question 27

proteoglycans

Answer 27

GAG chains covalently linked to a core protein

(collagen is a major protein in the ECM)

Question 28

how is the ECM produced?

Answer 28

secreted by cells
fibroblasts produce a large portion of connective tissue

Question 29

what is the basal lamina?

Answer 29

a special form of the ECM - a thin layer that lies beneath epithelial cells

Question 30

three ways the basal lamina is organised

Answer 30

1. surrounding cells (like muscle cells)
2. lie underneath sheets of epithelial cells
3. separating two sheets of cells (eg. epithelial / endothelial cells in the kidney glomerulus)

Question 31

what are features of GAGs?

Answer 31

highly charged –> stiff and highly hydrated

multiple units of sugar (repeating disaccharide sequence)

Question 32

describe the structure of fibrous collagen

Answer 32

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)

Question 33

describe the structure and function of fibronectin

Answer 33

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

Question 34

laminin

Answer 34

a multi-domain glycoprotein that binds to collagen, major component of the basal lamina and anchoring it to cells