The Cell-41 Flashcards
The cytoskeleton and cell-cell junctions
What are the advantages of multicellularity?
-Multicellular organisms can exploit resources that many single-celled organisms cannot.
-Even in the simplest multicellular organism, the cells co-operate.
-In a multicellular organism, cells become specialised.
-Cell interactions are crucial, allowing cells to assemble into tissues and to communicate.
How can cells combine in their millions to form large, very strong structures (e.g. animals)?
Their strength comes from:
-the strength of the internal cytoskeleton
-the cell-cell adhesions that tie the cytoskeletons of neighboring cells together
-the extracellular matrix (ECM)
What is the cytoskeleton?
Provides mechanical strength
Drives organelle movement
-i.e. secretory pathway organelles move along microtubules
Serves as an anchor for cell-cell junctions
-determines cell polarity
Drives chromosome segregation in mitosis and splits the cell in two (cytokinesis)
Enables cell movement and muscle contraction
What are the components of the cytoskeleton and their roles?
Microtubules:
-position and movement of organelles
-chromosome segregation
Actin filaments:
-cell shape
-cell movement
Intermediate fillaments:
-mechanical strength
Associated proteins (e.g. motor proteins)
What are cytoskeleton microtubules?
Stiff tubular structures made up of non-covalent heterodimers of alpha and beta tubulin subunits.
Both subunits bind GTP and GDP.
There is a polarity: a + end and a - end.
GTP-bound heterodimers bind only at + end.
Describe the growth and shrinkage of a microtubule.
Growth of a microtubule is unidirectional.
It grows and degrades from the + end only.
Shrinkage happens from the + end only and is extremely rapid if the end is bound to GDP.
Describe microtubules and how they are restructured.
Microtubules are dynamically unstable.
They are restructured very rapidly.
What is the function of microtubules?
Chromosome segregation. E.g. in mitosis.
Cytokinesis- restructuring internal network of daughter cells.
Position and movement of organelles.
What are actin filaments?
Non-covalent polymers of actin monomers.
Each monomer binds ATP (which is replaced by ADP in the filament).
The two filaments twist around each other to form an actin molecule.
There is polarity: a + end and a - end.
What is the function of actin?
Actin controls cell shape and movement.
The way actin molecules bind together effects the cell shape and movement.
How does actin grow?
Actin filaments can grow from both ends.
Describe the strength and flexibility of actin.
Actin molecules are more flexible than microtubules.
They can bundle together to form very strong structures.
Describe intermediate filaments.
Rope-like fibres:
-alpha helical monomers
-intermediate filament proteins
-coiled coils
-filaments
What are intermediate filaments?
Large and diverse family of non-nucleotide binding proteins.
E.g. nuclear lamins or epithelial keratins
What is the role of intermediate filaments?
Provide mechanical strength- they bend but do not break.
What is each cytoskeleton element made up of? What does this result in?
It is made up of several protein subunits.
Assembly and disassembly of these subunits results in growth/shrinkage of filaments and allows for rapid structural reorganisation.
What can cytoskeleton elements form? What does this influence?
Elements can form stable structures- cell-to-cell junctions.
They influence:
-cell to cell communication
-cell organisation
-developmental choices
What do desmosomes give? What do they contain? Where are they abundant?
Give epithelium mechanical strength.
Contain cadherins that connect intermediate filaments in one cell to those in the next cell.
Abundant in epithelia and in tissues that are subject to high mechanical stress.
What are adherens junctions? What do they allow?
They are cell-cell anchoring junctions.
They allow indirect linkage of the actin cytoskeletons of neighbouring cells.
What are cadherins?
They transmembrane proteins that form homodimers.
Extracellular polypeptides contain 5 cadherin domain repeats. There are Ca2+ binding sites between each one of the repeats.
There are many members in the cadherin superfamily (180 in humans).
How do cadherins interact?
Cadherins of the same type in the plasma membranes of adjacent cells will interact weakly (so each pair is easily disassembled).
However, having lots of interactions gives an overall strong attachment- velcro effect.
Homophilic binding.
What affects cadherin structure?
Loss of Ca2+.
Cells can’t communicate and are isolated.
What was the first cell adhesion study?
By Henry V.P. Wilson 1863-1939. In 1907:
Sponges were disaggregated into single cells by forcing pieces of sponge through a fine sieve (a ‘bloting cloth’), suspending the cells in a saucer of sea water and examining them using a microscope.
The individual cells moved like amoebae, aggregated together and sponges reformed/
What are sponges?
Sedentary marine animals, with no nervous system, belonging to the phylum, Porifera.
How did Wilson try to make a hybrid of the sponges? What did this show us?
Tried to make a hybrid from two different species by disaggregating cells and mixing them. He wasn’t able to form hybrids.
This shows that sponge cells recognise each other: they display homotypic recognition, but not heterotypic recognition.
Sponge cells display species - selective recognition.
Do other cells display selective recognition? Why?
Disaggregate and mix up the cells of an amphibian embryo, and they will sort themselves out again according to their origins.
Neural tube is internal.
Epidermis is outside.
Mesoderm is in between.
This is due to the specific cadherins expressed on each cell type, and this selective recognition is important for developmental tissue assembly programmes and repair.
What do adherens junctions coordinate? Why?
Coordinate the actin-based motility of adjacent cells. Indirectly links cells together.
This is because the adherin interactions indirectly link the actin cytoskeletons of adjacent cells via anchor/adapter proteins (e.g. catenins).
What happens to adherens junctions in epithelial cells? How is this different from other cells?
Form a continuous contractile ‘belt’ around epithelial cells. Multiple network connections forming a transcellular network.
Adherens junctions in many cells are small punctate attachment points.
What happens when adhesion belts tighten?
Can tighten to cause invaginations/tubulation of epithelial layers.
Invagination of epithelial sheet caused by an organised tightening along adhesion belts in selected regions of cell sheet.
Epithelial tube pinches off from overlying sheet of cells.
Give a summary of adherens junctions.
The cell-cell interacting membrane proteins are cadherins.
The homophilic interactions they make are weak, but many acting together makes for strong attachment points.
Cadherins enable cells to be recognised and to be segregated and sorted. Changes in cadherin expression affect this (important in development, tissue formation, cell migration and wound repair).
Abnormal expression of cadherins is connected to cancer metastasis, angiogenesis, adhesion and invasion.
The junctions connect indirectly to the actin cytoskeleton via catenins and so influence the coordinated contraction of cells (especially in epithelial layers).
There is a complex interplay between chemical signalling pathways and cell-cell adhesion.
What are focal adhesions?
Connect the ECM to the cytoskeleton.
What are integrins?
Transmembrane proteins that allow the internal cytoskeleton to grip onto molecules (not directly bound e.g. collagen and actin filaments) in the ECM when necessary.
How do integrins bind to ECM molecules?
Each integrin is an alpha/beta heterodimer than links an ECM to talin.
Talin links to actin. Other proteins reinforce the linkage.
Describe the types of inegrins.
There are 8 different beta chains and 18 different alpha chains. Each with distinct ligand binding properties (for different ECM components).
Has a wide combinational repertoire- can bind many molecules, not just 1 alpha and 1 beta.
How do integrins act as receptors for ECM molecules?
Like cadherins in cell-cell interactions, integrins bind ECM molecules with low affinity but there are many of them.
Interactions can be formed (e.g. epithelium cells binding to the basal lamina) and can also be released (e.g. when a fibroblast or macrophage crawls through a tissue).
An integrin must be able to switch from an active (ECM binding) to an inactive (non-ECM binding) state for a cell to migrate, and vice versa by changing its conformation at both ends of the cell membrane.
What is the importance of ECM interactions?
Cells need anchoring to the ECM to grow and proliferate. No binding exposes cells to stress (loss of growth stimuli, altered mechanical force, cytoskeletal reorganisation, reduced nutrient uptake ect).
Detached cells may die if contact with ECM is lost.
This is called anchorage dependence.
What is anchorage dependence mediated by?
Integrins and the signals they generate inside cells.
What are occluding (tight) junctions?
Don’t allow mixing, these cells are polarised. Relevant to epithelial cells.
Occluding junctions block the mixing of apical and basolateral membrane proteins to maintain cell polarity. Therefore different functions of membranes.
What is the importance of cell polarity?
It is functionally important e.g. in the gut it ensures a one-way movement of glucose from the gut lumen to blood.
Here, inward active transport of glucose is confined to apical surfaces while outward passive transport of glucose is confined to the basolateral membrane because the relevant transporters are separated and cannot intermix.
What do tight junctions look like?
Thin bands of integral plasma membrane proteins (claudin and occludin) encircle the cell. Rows of such proteins from neighbouring cells interlock to form a tight extracellular seal.
The rows of proteins also prevent lateral diffusion of lipids and proteins in the plasma membranes of the cells.
How is a passageway between cells formed?
Channel proteins (celled connexons- that are made up of 6 connexins) form adjacent plasma membranes and align to create homotypic or heterotypic channels between cells.
They connect 1 cell to another, big molecules cannot move through.
What are the roles of gap junctions?
-allow metabolic coupling and electrical coupling (useful wen cells need to be in sync e.g. heart/gut).
-smooth out any fluctuations in the concentrations of small molecules in neighbouring cells.
-help coordinate cell responses (e.g. in liver where many cells must respond to a nerve signal received by only a few of them).
-important where neurones need to act in synchrony, cell coupling by gap junctions in such cells allows action potentials to spread rapidly, avoiding delays at synapses.
