CBS - Cytoskeleton Flashcards
What is the cytoskeleton?
It is a network of protein filaments within a cell.
It has a range of functions:
- connection with Extracellular Matrix (ECM)
- maintaining cell shape
- intracellular transport
- cytokinesis
- chromosome separation
- cell movement
What three structures if the cytoskeleton composed of?
Actin mircofilaments
- they are olymers of actin
- they are 7-9 nm in diameter
Intermediate filaments
- they are composed of tissue-specific proteins
- they are 10 nm
Microtubules
- they are polymers of tubulin
- they have a 25 nm diameter
Describe actin microfilaments.
The monomer is a globular protein (called G-actin), which contains an ATP-binding domain.
G-actin polymerises to microfilaments (F-actin), and the process involves ATP hydrolysis.
The polymerisation occurs via non-covalent interactions, with the monomers in the head to tail orientation, and as a result each microfilament has a (+) and (-) end (i.e. it has polarity). Monomers can be added at both the (+) and (-) end.
It is a dynamic structure: its length depends on the relative rate of loss and gain of G-actin monomers.
The actin microfilaments are usually present as two tightly wound chains. It comprises ~5% of cellular protein.
What are the functions of actin?
- muscle contraction
- mechanical support
(the internal strength of microvilli is provided by actin filaments) - maintaining cell shape
(there are bands of actin that run parallel to the surface of the cell, helping it maintain its shape) - cell movement
What are the different actin binding proteins?
Actin binding proteins provide a function to the filaments.
G ACTIN BINDING PROTEINS:
- thymosin β4 : inhibits polymerisation
CROSS-LINKING PROTEINS:
- villin : crosslinks parallel bundles in microvilli
- filamin : joining the microfilaments at angles to create a mesh
SEVERING PROTEINS:
- gelsolin : cuts and binds (+) end; the other part depolymerises – “gel to sol”
How does contraction occur in non-muscle cells?
The muscle myosin is also present in non-muscle cells. The interaction between myosin and actin microfilaments allows for movement, and it requires ATP hydrolysis.
It also allows movement within cells (changes shape of cell). An example would be cytokinesis : a ring of actin forms in the centre of the cell, anchors to the plasma membrane, and myosin contraction constricts the cell.
Additionally, it also allows for the movement of cells. Lamellipodia, such an example, is mediated cell movement across the extracellular matrix (ECM).
How do lamellipodia form?
Extensions of cells project out, which contain an actin network. They are generated by the rapid growth of actin filaments at the cell membrane.
The tip of the lamellipodia interacts with the ECM via integrins.
The contraction involving myosin allows for cell movement.
Describe intermediate filaments (IF).
They are polymers of individual IF proteins - they are 10nm in diameter.
There are different IF proteins in different cell types
- in epithelia cells we have keratin(s), which provide physical support and external structures.
- in axons, we have neurofilamin(s), which provide a structural arrangement of axons
- in universal (nuclear) cells, we have lamins A, B, and C, which support the nuclear structure
They are usually stable and not dynamic (once formed, they are stable). However, lamins are an exception as the nuclear membrane reforms during mitosis.
How do IF polymers form?
We have the intermediate filament protein (which is the monomer).
It forms a helical dimer. The two dimers combine to form a tetramer (the fundamental unit of the IF).
The tetramers link in a staggered formation and end-to-end to form the filament.
Subunit exchange is slow but occurs throughout the length of the filament.
What are the interactions between IFs and the cytoskeleton?
IFs can link actin mircofilaments and microtubules
e.g. plectin
There are proteins that link together these different parts of the cytoskeleton.
What are some clinical considerations to do with intermediate filaments?
Mutations in keratins can result in the skin blistering disease epidermolysis bullosa simplex (EBS).
Abnormal expression of neurofilamins can result in the neurodegenerative disease amyotrophic lateral sclerosis (ALS).
Describe microtubules.
The tubulin monomer is a heterodimer: α-tubulin and β-tubulin. A protofilament is a long chain of alternating tubulin monomers.
The protofilament has a (-) and (+) end. Monomers can be rapidly added and removed from both (+) and (-) ends.
13 parallel protofilaments are arranged in a hollow tube. The microtubules are approx. 25nm in diameter.
Describe Microtubule-Organising Centres (MTOC).
Microtubules usually have one end attached to a Microtubule-Organising Centre (MTOC). Microtubules “grow out” from MTOC until they reach their destination and then are stabilised.
One major MTOC is associated with the nucleus.
What are the functions of microtubules?
They are a dynamic scaffold:
- they make up the spindle for chromatid separation during mitosis
They can move cargo to specific locations in the cell.
They are the central internal support of cilia.
They stabilise structure of cells e.g. platelets
They organise the structure of organelles
e.g. endoplasmic reticulum.
Describe the spindle formation.
The spindle consists of microtubules. The spindle formation is initiated from the centrosome (which is a type of Microtubule-Organising Centre).
Centrosomes contain a pair of centrioles. Centrioles contain stable fused microtubules (so they are slightly modified microtubules).
Centrosomes form at two poles of cell. Kinetochore microtubules attach to the centromere of chromatid. Additional aster microtubules attach the centrosome to cell membrane, and thus the spindle is formed.
