The Cytoskeleton Flashcards
What is the cytoskeleton?
The skeleton of the cell
A cell needs its cytoskeleton to keep its shape and modify it in response to environmental cues
What is the structure of the cytoskeleton like?
It is a complex network made of 3 different polymers: Microtubules Intermediate filaments Actin filaments They provide for: Shaping of the cell Intracellular movement of organelles Cell movement
What are the main functions of each network?
Microtubules: Organelle positioning Intracellular transport Intermediate filaments: Mechanical strength Actin filaments: Cell shape Organelle shape Cell migration
Why is the cytoskeleton dynamic? What do accessory proteins do to support this?
The cytoskeleton is dynamic and this is facilitated by its organisation
Polymers are made of monomers
Monomers are very abundant and not covalently linked and this allows for easy movement around the cell
Accessory proteins regulate:
Site and rate of filament formation (nucleation)
Polymerisation/ depolymerization
Function
What is the structure of actin filaments like?
Twisted chain of units (monomers) of the protein actin (G-actin)
This chain constitutes the filamentous form (F-form)
Thinnest class of the cytoskeleton filaments (7nm)
Presents structural polarity
At the positive end, most of the monomers are added whereas at the minus end the addition of monomers is less favourable
Associated with a large number of actin-binding proteins (ABP)- variety of organisation and function
There are 3 isoforms of G-actin with different isoelectric points:
Alpha-actin found mainly in muscle cells
Beta and gamma-actin in non-muscle cells
What is actin polymerisation?
Actin filaments (F-actin) can grow by addition of actin monomers (G-actin) at either end
The length of the filament is determined by:
Concentration of G-actin
Presence of Actin Binding Proteins (ABPs)
How do ABPs work on G-actin compared to F-actin
ABP: Proteins binding to monomers
G-actin levels are controlled mainly by 2 ABPs:
Profilin- facilitates actin polymerisation
Thymosin beta4- prevents the addition of actin monomers to F-actin
ABP: Proteins binding to filaments
Actin bundling proteins:
Keep F-actin in parallel bundles ( as in the microvilli observed in epithelial cells)
Cross-linking proteins:
Maintain F-actin in a gel-like meshwork (as seen in the cell cortex, underneath the plasma membrane)
F-actin severing proteins:
break F-actin into smaller filaments
Motor proteins (myosin):
Transport of vesicles and/or organelles through actin filaments
What are the specific functions of the actin filaments
Skeletal muscle:
Arranged in a para-crystalline array integrated with different ABPs
Interaction with myosin motors allow muscle contraction
Non-muscle cells:
Cell cortex- form a thin sheath beneath the plasma membrane
Associated with myosin form a purse-string ring resulting in cleavage of mitotic cells
Cytokinesis- involvement of an actin-myosin ring
Cell migration (a multi-step process)
How does cell migration happen through actin filaments?
The cell pushes out protrusions at its front (lamellipodia and filopodia)
Occurs through actin polymerisation
These protrusions adhere to the surface
Integrins link the actin filaments to the extracellular matrix surrounding the cell
Cell contraction and retraction of the rear part of the cell
Interaction between actin filaments and myosin
What is the structure of the intermediate filaments like?
Toughest of the cytoskeletal filaments (resistant to detergents, high salt etc.)
Rope-like with many long strands twisted together and made up of different subunits
Intermediate size (8-12nm)
Forms a network:
Throughout the cytoplasm, joining up to cell-cell junctions (desmosomes)
Withstands mechanical stress when cells are stretched
And surrounding nucleus
Strengthens the nucleus envelope
What is the polymerisation of intermediate filaments like?
Each unit is made of: N-terminal globular head C-terminal globular tail Central elongated rod-like domain Units form stable dimers Every 2 dimers forma tetramer Tetramers bind to each other and twist to constitute a rope-like filament
What are the different types of intermediate filaments?
These categories are split according to the protein units it is made of and their localisation
Cytoplasmic:
Keratins (in epithelia)
Vimentin and vimentin-related (in connective tissue, muscle cells and neuroglial cells)
Neurofilaments (in nerve cells)
Nuclear:
Nuclear lamins (in all nucleated cells)
What are the intermediate filaments binding proteins (IFBP)?
Main linker of IF structures
IFBP stabilise and reinforce IF into 3D networks
Examples:
Filaggrin- binds keratin filaments into bundles
Synamin and Plectin- bond desmin and vimentin
Link IF to the other cytoskeleton compounds (i.e. actin and microtubules) as well as to cell-cell contact structures (desmosomes)
Plakins- keep the contact between desmosomes of epithelial cells
What is the function of the intermediate filaments in the cytoplasm?
In the cytoplasm they provide:
Tensile strength- this enables the cells to withstand mechanical stress (to stretch)
Structural support- by creating a deformable 3D structural framework and reinforcing cell shape and fix organelle localisation
What re the functions of the intermediate filaments 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
Provide attachment sites for chromatin
Disassemble and reform at each cell division as nuclear envelope disintegrates i.e. very different from the stable cytoplasmic IFs
Process controlled by post-translational modifications (mainly phosphorylation and dephosphorylation)
