E. Basic Molecular Biology - Interaction between cells Flashcards
Cell Adhesion:
2 main categories =
- cell to cell
- Cell to extracellular matrix
4 main types of permanent cell junctions:
adherens junctions
Desmosomes
Tight junctions
Gap junctions
Similarities in cell-cell adhesion in adherens junctions and desmosomes:
- intracellular cytoskeletal filaments of adjacent cells are joined by means of special membrane
structures
Similarities in cell-cell adhesion in adherens junctions and desmosomes:
- intracellular cytoskeletal filaments of adjacent cells are joined by means of special membrane
structures
What do actin filaments do?
- determine shape of cell surface and responsible for locomotion
What is the role of intermediate firmaments eg. Keratin? (2)
- provide mechanical strength
- Bundles of fibres join the cell membranes
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
motility
intermediate
Cell-to-cell adhesion junctions:
- both types of junctions (adherens and desmosomes) use the same family of transmembrane adhesion proteins: cadherins
What are cadherins? (6)
- 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)
General scheme to adherens junctions and desmosomes: (2)
- 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
What is B catenin? (4)
- 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
Mechanism used for cell-matrix adhesion: (2)
- proteins used are integrins
- Bind actin and intermediate filaments (esp keratin)
What are Integrins? (4)
- 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
Integrins always recognise the same sequence of aa (RGD)
Binding cytoskeleton to basement membrane (extracellular matrix) > ________
_______ > antibody components of hemidesmosome
hemidesmosome
Pemphigoid
Integrins always recognise the same sequence of aa (RGD)
Binding cytoskeleton to basement membrane (extracellular matrix) > ________
_______ > antibody components of hemidesmosome
hemidesmosome
Pemphigoid
Effect of binding to ECM on intracytoplasmic portion of integrin: (2)
- activate from inside or outside
- Outside in > binding of something on the outside initiating the inside of the integrin
Effect of binding to ECM on intracytoplasmic portion of integrin —->
- Effects of outside - in activation: (5)
- 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
- Inside out ___ change inside (anchor binding) and leads to activation of outside
>
Transient adhesion and cell migration: (2)
- adhesion that can be formed and broken down (allowing cells to crawl
through ECM) - Undergoes inside out deactivation
Cell-to-cell adhesion using integrins: (5)
- 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
Tissue dynamics
Growth and turnover of tissues require: (4)
- proliferation
- Differentiation
- Maturation
- Cell death
● precisely controlled in terms of space and time
How proliferation is controlled:
Drivers of proliferation and ______ inhibitors
growth
How proliferation is controlled:
Drivers of proliferation and ______ inhibitors
growth
What is differentiation? (3)
- 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”
What is Maturation? (2)
- process of becoming a fully functional cell
- Occurs once there is complete commitment
to a specific lineage
What is Haemopoiesis?
- haemopoietic system as an illustration of
differentiation and maturation
Cell fate depends on the receptor it expresses and the growth factors it encounters
Growth factors: (4)
- 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
Cell fate depends on the receptor it expresses and the growth factors it encounters
Maturation: (3)
- occurs after commitment
- First recognisable cell = blast
- Cross over in proliferation and maturation
Capacity to proliferate
Transit amplification cells > able to proliferate actively Mature cells > usually __ ____ proliferate
do not
What is the intestinal villus? (3)
- 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
What is the Muscle satellite cell? (4)
- 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
Defining characteristics of stem cells: (2)
- 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
What are the types of stem cells? (2)
- embryonic
- Adult > in all tissues and specific for each type, more differentiated than embryonic stem cell
How are stem cells maintained? (3)
- 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)
- The stem cell niche (the microenvironment) : (4)
- 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)
How does the stem cell produce daughter cells with differing fates? (3)
- 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
