Week 9 (cytoskeleton) Flashcards
What is the cytoskeleton?
an intricate network of protein filaments that extends throughout the cell
What are the Functions of the cytoskeleton?
-Controlling the location of the organelles
•Providing machinery for transport between organelles
•Segregating chromosomes into two daughter cells at cell division and pinching apart those two new cells
Cytoskeleton proteins- What are actin filaments?
- The thinnest filaments of the cytoskeleton, a structure found in the cytoplasm of cells. These linear polymers of actin subunits are flexible and relatively strong, resisting buckling due to compressive forces and filament fracture by tensile forces on the cells.
- Each actin molecule has binding sites for Mg2+ ion with either ATP or ADP bound.
- Actin exists in two principal forms, i.e. globular monomeric form (G) and filamentous polymeric form (F).
Describe the regulation of Actin- Actin Binding Proteins:
Motor proteins
e.g. Myosin
Move along actin filaments carrying a cargo
Regulation of Actin- Actin Binding Proteins: Crosslinking proteins
e.g. α actinin
Crosslink actin into higher-order assemblies or to other structures, such as plasma membrane
Regulation of Actin- Actin Binding Proteins: Nucleating
e.g. Formin
Initiating the formation of new filaments as branched networks
Regulation of Actin- Actin Binding Proteins: capping
Caps filament ends to prevent polymerization
Regulation of Actin- Actin Binding Proteins: monomer binding
Profilin: binds to actin monomer and accelerates elongation
Thymosin: binds and locks actin monomer
Cofilin: binds and destabilizes ADP-actin filaments (depolymerization)
Regulation of Actin- Actin Binding Proteins: Filament binding
e.g. Tropomyosin
Stabilizing filament
Regulation of Actin- Actin Binding Proteins: severing e.g thymosin
Depolymerizing actin filament
Cytoskeleton proteins- Actin Filaments: cellular functions
Determines the shape of the cell’s surface
•Whole-cell locomotion
•Cell division
Cytoskeleton proteins- Actin Filaments: Physiological functions (in association with Actin Binding proteins)
Body muscle contraction
•Heart function
Cytoskeleton proteins- Actin Filaments: Dysfunctions
Congenital myopathies
•Actin-accumulation myopathy (severe muscle weakness (myopathy) and poor muscle tone (hypotonia) throughout the body)
Cytoskeleton proteins- Microtubules
Filaments
Filaments
•Microtubules
A component of the cytoskeleton, found throughout the cytoplasm. These tubular polymers of tubulin can grow as long as 50 micrometres and are highly dynamic. The outer diameter of a microtubule is about 24 nm while the inner diameter is about 12 nm.
Cytoskeleton proteins- Microtubules
Structure of microtubules
Structure of microtubules
•There are two types of tubulin molecules, α tubulin and β tubulin, which form a heterodimer.
•Both α monomer and β monomer can bind to GTP. GTP bound to the α-tubulin is trapped at the dimer interface and is never hydrolysed or exchanged, while the β-tubulin can bind to either GTP or GDP.
Stabilizing MAPs
MAP2: binds along the microtubule lattice and stabilizes microtubules
Tau: possesses a microtubule crosslinking domain
Plectin: links to intermediate filaments
What are MAPs?
Microtubule Associated proteins
Destabilizing MAPs
E.g. Stathmin: binds tubulin dimers prevents assembly
Katanin: severs microtubules
MAPs: Plus end track protein
XMAP215: stabilizes plus ends and accelerates assembly
Plus end tracking proteins (+TIPs): remain associated with growing plus ends and can link plus ends to other structures
MAPs: Motor Proteins
E.g. Kinesins and Dyneins, transport cargo and perform a variety of other cellular functions.
Which Specialized Organelles are associated with microtubules?
Cilia and centrioles
Cytoskeleton proteins- Microtubules: cellular functions
Localizing and transporting organelles
•Cell division
Cytoskeleton proteins- Microtubules: physiological functions
Neuron migration
•Motile cilia: clearing dirt, dust, micro-organisms and mucus, to prevent disease
Cytoskeleton proteins- Microtubules: dysfunctions
Alzheimer’s disease (Hyperphosphorylation of Tau)
Cytoskeleton proteins-Intermediate Filaments
Describe their properties compared to other filaments
-With an average diameter of 10 nanometers, which is between that of 7 nm actin (microfilaments), and that of 25 nm microtubules, and they were initially designated ‘intermediate’ because their average diameter is between those of narrower microfilaments (actin) and wider myosin filaments found in muscle cells.
-Their core structure is an α-helical coiled coil.
Intermediate filaments are prominent in cytoplasm of cells that are subject to mechanical stress.
Cytoskeleton proteins-Intermediate Filaments
Describe their structure
Structure of Intermediate Filaments
•All intermediate filament family members are elongated proteins with a conserved central α-helical domain.
•The assembled intermediate filament lacks the overall structural polarity (no plus or minus ends)
•Intermediate Filaments do NOT contain a binding site for nucleotide
•Intermediate filament proteins consist of two globular head groups separated by an extended polypeptide chain
•The actual mechanism of assembly and disassembly of intermediate filaments is less understood, compared to actin and microtubules. But it is known that they are regulated by phosphorylation
Cytoskeleton proteins-Intermediate Filaments
Give examples of different classes
- Keratin: epithelial cells
- Vimentin and vimentin-related filaments: connective tissue cells, muscle cells and supporting cells of the nervous system
- Neurofilament: nerve cells
- Nuclear lamins: strengthen the nuclear envelope
Cytoskeleton proteins-Intermediate Filaments: cellular functions
Cellular functions
•The mechanical stability of the plasma- and the nuclear membrane
•Cell-cell interaction
Cytoskeleton proteins-Intermediate Filaments: physiological functions
Neuron
•Development and regeneration
•Ageing
Cytoskeleton proteins-Intermediate Filaments: dysfunctions
Progeria (caused by lamin A gene mutation that causes children to age rapidly)
What are the different types of cytoskeleton filaments?
Actin filaments
Microtubules
Intermediate filaments
Advantage of cross linking to create a bundle?
Stronger= more resistance to stress
What binds to actin?
ATP/ADP
What are filaments?
Long chains of proteins, such as those found in hair, muscle or -flagella.
Why are filaments often bundled together?
For strength and rigidity
What are the proteins that make up the filaments of cytoskeleton?
- Actin filaments
- Intermediate filaments
- Microtubules
Is Tubulin a globular or fibrous?
Globular
Is the GTP bound to alpha Tubulin hydrolysed?
No
It is needed for structure
Is the GTP bound to beta Tubulin hydrolysed?
Yes after it is added on to the microtubules
Which filaments don’t have plus and minus ends?
Intermediate filaments
Which filaments dont have binding sites for nucleotides such as ATP?
Intermediate filaments
