Cytoskeleton Flashcards
Why does a cell need a cytoskeleton?
To keep its shape and modify it in response to environmental cues
What in cells needs to be organised by the cytoskeleton?
Cells contain proteins organised in filamentous structures involved in:
- establishing cell shape
- providing mechanical strength
- cell movement
- chromosome separation
- intracellular transport of organelles
How is the cytoskeleton structured?
- it is constituted of filamentous structures
- there are 3 types:
1. Actin filaments (microfilaments)
2. Intermediate filaments
3. Microtubules - also uses a large number of accessory proteins to maintain and regulate the properties associated with the filaments
- each type of filament has distinct mechanical properties and dynamics, but certain fundamental properties are common
What are the cytoskeleton’s accessory proteins?
- cytoskeleton binding proteins
- cytoskeleton association proteins
- motor proteins
They regulate:
- site/rate of filament formation (nucleation)
- polymerisation or depolymerisation
- function
What level of deformation do the 3 filaments exhibit?
- actin = low level with a medium force
- intermediate = very high level with a high force
- microtubules = high level with a very low force
What are the protein subunits for each filament?
- actin = actin monomer
- intermediate = various proteins with an alpha helical coiled coil
- microtubule = tubulin heterodimer
What is the bound nucleotide for each filament?
- actin = ATP
- intermediate = none
- microtubules = GTP
What is the dynamic instability of each filament?
- actin = no
- intermediate = no
- microtubules = yes
Is the cytoskeleton dynamic?
- it is dynamic and is facilitated by its organisation
- this contains polymers made from monomers which are very abundant and aren’t covalently linked
- this does not mean it is chaotic
What are intermediate filaments?
- present in nearly all animals but absent from plants and fungi
- rope like network of filaments in the cell
- main function is maintenance of cell structure by providing tensile strength to the cell
What is the structure of an intermediate filament?
- starts with an alpha-helical region monomer
- two of these coil together to form a coiled-coil dimer
- two of these come together to form a staggered tetramer
- eight tetramers twist together to form the filament
How do intermediate filaments differ from actin and microtubules?
- do not have a defined polarity (no +/- ends)
- do not have associated motor proteins
- do not bind to nucleotides (ATP/GTP)
- very stable compared
How is tissue specific expression of IF proteins useful for diagnostics?
- IF gene expression is often unaffected
- cancer cells lose the characteristic shape of the parent tissue
- identification of IF proteins in tumour biopsies using antibodies can pinpoint origin of tumours (eg neurofilaments in metastatic cells from brain cancer)
What are the 4 type of IF proteins?
- Keratins - in epithelia
- Vimentin - in connective tissue, muscle cells, neuroglial cells
- Neurofilaments - in nerve cells
- Nuclear lamins - in all animal cells
What is the function of the IF proteins?
provide tensile strength in the cytoplasm which allows cells to withstand mechanical stress (and stretch)
What is the function of keratin?
- found in stratified squamous epithelium
- stem cells in the interior
- dead cells at outermost surface
- keratin remains - hard, waterproof resists abrasions
- makes up hair, nails, skin, feathers
- keratin forms a strong network through indirectly linking to neighbouring cells
- disruption of this results in blistering
What do hemidesmosomes do?
- mediate cell matrix adhesion between epithelial cells and basal lamina
- integrins alpha6beta4 binds to proteins in the plaques and to laminin in the extracellular matrix
What is the function of vimentin?
- present in connective tissue and muscles
- require trans-epithelial migration (ability of WBCs to leave blood to combat infection)
- process is impaired in vimentin mutant mice
What is the function of desmin?
- tethered to the Z disk
- develop the sacromere
- do not participate in contraction but maintain structural integrity
- mutant mice have misaligned muscle fibres
- mutations in human desmin causes muscle disorders
What is the function of neurofilaments?
- present in neurons
- important for nervous system function
- unlike other IF, they have side arms that project from the core filament
- fill and pack the cytoplasm of neurons
- neurons in KO mice make axons with smaller diameters
- Charcot-Marie-Tooth disease = neuropathy where peripheral nervous system degenerates
What are the functions of the IFs in the nucleus?
- present in all nucleated eukaryotic cells
- form mesh rather than rope like structure
- line in the inner face of the nuclear envelope to strengthen it and to provide attachment sites for chromatin
- disassemble and reform at each cell division as nuclear envelope disintegrates
What is the function of nuclear lamins?
- present in the nuclei of all cells
- form a basket like structure on inner side of nuclear membrane that protects the structure of the nucleus
- disassemble when cells enter mitosis
What are the IF binding proteins (IFBPs)?
- mainly linkers of IF structures
- stabilise and reinforce IFs into 3D networks
- examples:
1. Fillagrin = binds keratin filaments into bundles
2. Synamin and Plectin = bind desmin and vimentin, link IF to other cytoskeleton compounds (ie actin and microtubules) as well as to cell-cell contact structures (desmosomes)
3. Plakins = keep the contact between desmosomes of epithelial cells
What is the function of microtubules?
- organised to perform specific functions
- establish an internal polarity to movements and structures in the interphase cell
- participate in chromosome segregation during cell division
- establish cell polarity during cellular movement
- produce extracellular movement via beating of cilia and flagella
What is the structure of a microtubule?
- alpha-tubulin and beta-tubulin join to form a tubulin heterodimer
- many of these join in a linear structure to form a protofilament which has a + and a - end
- the protofilament is structured so that there is a lumen down the middle
- the subunit addition takes place predominantly at the + end
- they have a cap of GTP at the + end
Do microtubules exhibit dynamic instability?
- the total mass of polymerised tubal in remains constant but individual microtubules are dynamic
- growth = assembly of microtuble
- shrinkage = disassembly of microtubule
- catastrophe = switching from growth to shrinking
- rescue = switching from shrinking to growth
