E. Basic Molecular Biology - Interaction between cells

Question 1

Cell Adhesion:
2 main categories =

Answer 1

• cell to cell
• Cell to extracellular matrix

Question 2

4 main types of permanent cell junctions:

Answer 2

adherens junctions
Desmosomes
Tight junctions
Gap junctions

Question 3

Similarities in cell-cell adhesion in adherens junctions and desmosomes:

Answer 3

• intracellular cytoskeletal filaments of adjacent cells are joined by means of special membrane
  structures

Question 4

Similarities in cell-cell adhesion in adherens junctions and desmosomes:

Answer 4

• intracellular cytoskeletal filaments of adjacent cells are joined by means of special membrane
  structures

Question 5

What do actin filaments do?

Answer 5

• determine shape of cell surface and responsible for locomotion

Question 6

What is the role of intermediate firmaments eg. Keratin? (2)

Answer 6

• provide mechanical strength
• Bundles of fibres join the cell membranes

Question 7

Actin and intermediate filaments need to join to equivalent fibres in adjacent cells:

• adherens junctions bind actin of adjacent cells to coordinate ______ and activity
• Desmosomes bind _________ filaments of adjacent cells to provide mechanical strength

Answer 7

motility
intermediate

Question 8

Cell-to-cell adhesion junctions:

Answer 8

• both types of junctions (adherens and desmosomes) use the same family of transmembrane adhesion proteins: cadherins

Question 9

What are cadherins? (6)

Answer 9

• many members
• Highly tissue specific
• Attachment is stabilised by Ca2+
• Cadherin - transmembrane protein meeting with hook arrangement in the middle
• Single adherens junction of desmosomes is made of a cluster of numerous cadherin pairs
• Attach indirectly to cytoskeleton > anchor proteins bind cadherin to intracellular filament (include B catenin)

Question 10

General scheme to adherens junctions and desmosomes: (2)

Answer 10

• transmembrane cadherins bind by means of extracellular domain to identical
  cadherins on neighbouring cell
• Intracellular domain binds by means of specific anchor proteins to the
  cytoskeleton

Question 11

What is B catenin? (4)

Answer 11

• transcription factor in WNT pathway
• If it is taken up by formation of adherens junctions then it is unable to function
  as a transcription factor, reduction in WNT pathway activation
• Contributes to contact inhibition > when cells meet, Join and form adherens junctions they stop
  dividing. Important feature esp in epithelia
• Pemphigus > antibodies to cadherins of skin, skin cells do not adhere properly thus form blisters and peel off

Question 12

Mechanism used for cell-matrix adhesion: (2)

Answer 12

• proteins used are integrins
• Bind actin and intermediate filaments (esp keratin)

Question 13

What are Integrins? (4)

Answer 13

• alpha and beta subunit combine to form binding site for extracellular protein
• Beta subunit anchors to filaments inside cell (not direct > connects to anchor protein)
• Bind specific sequences in ECM molecules (RGD) by means of binding site
  from both chains
• Family - 18 alpha and 8 beta chains > can combine in diff ways to change properties and functions

Question 14

Integrins always recognise the same sequence of aa (RGD)

Binding cytoskeleton to basement membrane (extracellular matrix) > ________

_______ > antibody components of hemidesmosome

Answer 14

hemidesmosome
Pemphigoid

Question 15

Integrins always recognise the same sequence of aa (RGD)

Binding cytoskeleton to basement membrane (extracellular matrix) > ________

_______ > antibody components of hemidesmosome

Answer 15

hemidesmosome
Pemphigoid

Question 16

Effect of binding to ECM on intracytoplasmic portion of integrin: (2)

Answer 16

• activate from inside or outside
• Outside in > binding of something on the outside initiating the inside of the integrin

Question 17

Effect of binding to ECM on intracytoplasmic portion of integrin —->

• Effects of outside - in activation: (5)

Answer 17

• Binding of ligands to extracellular domain leads to changes in intracellular domains, can activate a number of pathways (eg. MAPK)
• Cells often require co-stimulation of integrin activation for full activation of other pathways
• Activation recruits kinases which phosphorylates nearby proteins creating docking sites for many signalling proteins
• No docking = no signalling
• Consequences of facilitation of signalling > most cells need to be attached to the ECM to survive and proliferate > anchorage dependence for cell survival

Question 18

• Inside out ___ change inside (anchor binding) and leads to activation of outside

Answer 18

>

Question 19

Transient adhesion and cell migration: (2)

Answer 19

• adhesion that can be formed and broken down (allowing cells to crawl
  through ECM)
• Undergoes inside out deactivation

Question 20

Cell-to-cell adhesion using integrins: (5)

Answer 20

• mediated by adhesion of an integrin to a member of the immunoglobulin superfamily/ICAM group of proteins
• Transient association
• Does not connect the cytoskeleton
  (only cell surface)
• Eg. Neutrophils and endothelium
• Inside out activation of integrin

Question 21

Tissue dynamics
Growth and turnover of tissues require: (4)

Answer 21

• proliferation
• Differentiation
• Maturation
• Cell death
  ● precisely controlled in terms of space and time

Question 22

How proliferation is controlled:
Drivers of proliferation and ______ inhibitors

Answer 22

growth

Question 23

How proliferation is controlled:
Drivers of proliferation and ______ inhibitors

Answer 23

growth

Question 24

What is differentiation? (3)

Answer 24

• process of becoming different from parent cell in order to develop a more distinct form and function within a tissue
• Embryo gives rise to differentiated cells such as muscle, skin and neurons during development form single undifferentiated cell
• Terms associated with this include “lineage”, “commitment” and “hierarchy”

Question 25

What is Maturation? (2)

Answer 25

- process of becoming a fully functional cell - Occurs once there is complete commitment to a specific lineage

Question 26

What is Haemopoiesis?

Answer 26

- haemopoietic system as an illustration of differentiation and maturation

Question 27

Cell fate depends on the receptor it expresses and the growth factors it encounters Growth factors: (4)

Answer 27

- lineage specific with some redundancy - Required for survival at all stages of differentiation and maturation - Required for proliferation - Eg. IL3, erythropoietin, thrombopoietin, GM-CSF, G-CSF

Question 28

Cell fate depends on the receptor it expresses and the growth factors it encounters Maturation: (3)

Answer 28

- occurs after commitment - First recognisable cell = blast - Cross over in proliferation and maturation

Question 29

Capacity to proliferate Transit amplification cells > able to proliferate actively Mature cells > usually __ ____ proliferate

Answer 29

do not

Question 30

What is the intestinal villus? (3)

Answer 30

- regenerated every 3 to 5 days - with cells of 4 lineages (enterocytes, goblet, enteroendocrine and Paneth cells) - All come from same stem cell - When TA cells reach the top of the crypt they stop proliferating, then differentiate and position themselves

Question 31

What is the Muscle satellite cell? (4)

Answer 31

- allows to replace and repair muscle fibres - Activation by, 1. NO (nitric oxide), 2. Growth factors, 3. ECM - Nitric oxide release is signal to initiate division (release ends suddenly) - Starts to divide to replace damaged cell

Question 32

Defining characteristics of stem cells: (2)

Answer 32

- Self renewal - unlimited or prolonged ability to produce a daughter cell which is identical to the parent - At least one type of highly differentiated descendant

Question 33

What are the types of stem cells? (2)

Answer 33

- embryonic - Adult > in all tissues and specific for each type, more differentiated than embryonic stem cell

Question 34

How are stem cells maintained? (3)

Answer 34

- prevention of differentiation and inappropriate proliferation - Factors intrinsic to the stem cell (eg activation of certain TFs and pathways) - The stem cell niche (the microenvironment)

Question 35

- The stem cell niche (the microenvironment) : (4)

Answer 35

- Ext signals controlling stem cell fate - Cell-cell interactions mediated by integral membrane proteins - Integrins and ECM. Integrins hold cells within a niche. ECM can modulate conc of growth factors - Secreted factors (Wnt ligands, TGFB)

Question 36

How does the stem cell produce daughter cells with differing fates? (3)

Answer 36

- asymmetric cell division - One daughter cell is excluded from the niche > comes under influence of a diff microenvironment - One daughter cell receives more of a fate-inducing factor