Lecture 18 Intercellular Signal Trafficking

Question 1

Signal transport mechanisms

Answer 1

1. Diffusion
2. Transcytosis
3. Exovesicle
4. Cytoneme

Question 2

Passive diffusion

Answer 2

Diffusion gradients
Reaches equilibrium
Physical flow of material

Question 3

Challenges of signalling through diffusion

Answer 3

Secretion from source cell
Interaction with matrix
Interaction with receptors and uptake in target cells
Degradation of ligand
Release of ligand from target cell

Question 4

Characteristics of diffusion based transport

Answer 4

Long life time of ligand in extracellular space
Short intracellular life time of ligand
Limited control of conc of ligand in cell
No control of direction

Question 5

What influences diffusion

Answer 5

The extracellular matrix

Question 6

The extracellular matrix influences diffusion by

Answer 6

Hindering diffusion
Complexing
Cell interactions

Question 7

Proteoglycans can regulate

Answer 7

the Fgf signalling pathway

Question 8

Fgf

Answer 8

Fibroblast Growth Factors

family of cell signalling proteins involved in development and regeneration

Question 9

Fgf’s are released locally upon

Answer 9

Injury

Question 10

HSPGs

Answer 10

Heparin sulfate proteoglycans

components of the ECM

Question 11

HSPGs mediate

Answer 11

Fgf signal transduction by acting as receptors or co receptors
regulate Fgf receptor trafficking
control secretion of Fgf ligands
regulate the structure of the ECM and establishment of Fgf signalling gradients (through hindered diffusion)

Question 12

RCM

Answer 12

Restrictive clearance molecule

describes the transport of a ligand through a tissue

Question 13

In the RCM extracellular ligand concentration is reduced which leads to

Answer 13

continuous degradation to maintain a concentration gradient

Question 14

In RCM the rate of uptake determines the

Answer 14

Gradient:
Decreased uptake = long term spreading
Increased uptake = short range spreading

Question 15

Fgf8 example of DIFFUSION

Answer 15

Rate of Fgf8 endocytosis and degradation determines the signalling gradient

Fgf8 is taken up by Rab5 (GTPase) increased activity of Rab5=shorter range for Fgf8

Question 16

Planar Transcytosis

Answer 16

Transport of a ligand THROUGH cells

continuous uptake, degradation and recycling with secretion

Question 17

The rate of endocytosis regulates the

Answer 17

Spreading

Question 18

Dpp example of TRANSCYTOSIS

Answer 18

Dpp = decapentaplegic signalling factor
regulates cell fate
Taken up by Rab5

Dpp is taken up by Rab5 increased activity of Rab5=shorter range for Dpp

Question 19

Exovesicles

Answer 19

Exosomes

Lipid bilayer contains lipids, nucleic acids, signalling and cellular proteins

Question 20

Exosome secretion pathway

Answer 20

Multi vesicular bodies are released as exosomes into the extracellular space
ESCRT complex important for exosome formation

Question 21

ESCRT is a protein complex that is

Answer 21

Highly conserved in eukaryotes

Question 22

ESCRT

Answer 22

Intracellular sorting machinery

Complex of 4 proteins

Question 23

ESCRT complex

Answer 23

ESCRT 0 - sequesters TM proteins in endosome
ESCRT 1,2 - causes membrane deformation into buds
ESCRT 3/Vsp4 - vesicle scission

All form a star like shape that bubbles the exosome

Question 24

Filopodia

Answer 24

Cytoplasmic fingers of actin

functions: movement, sensing, cell-cell signalling

Question 25

Signalling filopodia are called

Answer 25

Cytonemes

Question 26

Cytonemes are like

Answer 26

Arms that transport components of signalling machinery

Question 27

Filopodia formation

Answer 27

Initiation phase Protrusion phase Retraction phase

Question 28

Filopodia intiation phase

Answer 28

Nucleation complex | cdc42+IRSP53+Bar proteins bend the membrane

Question 29

Filopodia protrusion phase

Answer 29

cdc42 causes Actin filaments stabilise protrusions Growth by actin incorporation at the tip (mysoin10 transports actin to tip) Fascin connects actin filaments into bundles

Question 30

Wnt cytonemes

Answer 30

have an initiation, protrusion and retraction phase | Causes signalling in the recipient cell

Question 31

The Shh gradient (sonic hedgehog)

Answer 31

Limb bud development | Low to high conc = thumb to little finger!

Question 32

Shh is transported on

Answer 32

Cytonemes | Long signalling range as filopodia are very long

Question 33

DIFFUSION summary

Answer 33

1. Target cells control gradient by uptake 2. RCM 3. Signal interacts with ECM 4. Undirected, slow transport 5. E.g. Fgf, Egf, Nodal

Question 34

PLANAR TRANSCYTOSIS summary

Answer 34

1. Repetitive process of secretion and uptake 2. Target cell controls gradient by degradation and release of signalling proteins 3. Fast, directed transport 4. E.g. Dpp

Question 35

EXOVESICLE summary

Answer 35

1. Complex, includes MVBs and ESCRT machinery 2. Undirected transport 3. Difficult to get through epithelium 4. Found in bodyfluids, biomarker 5. E.g. Wnt, Shh

Question 36

CYTONEMES summary

Answer 36

1. Complex, requires filopodia 2. Source cell controls gradient (direction and length of cytonemes) 3. Fast and directed transport 4. Signal specificity (specific cytonemes for specific molecules 5. E.g. Wnt, Shh, Fgf

Question 37

Biomarker

Answer 37

A naturally occurring molecule, gene, or characteristic by which a particular pathological or physiological process, disease, etc. can be identified