Cytoskeleton: Intermediate filaments & Microtubules Flashcards
What does the cytoskeleton allow ?
Allows shape alteration, internal organisation, motility and mechanical
interaction with environment
What are the 3 main components of cytoskeleton?
Intermediate filaments, microtubules and actin filaments
Where is the Cytoskeleton ?
Present in bacteria but not as prominent or complex
Functions of Cytoskeleton ?
- Highly dynamic structure
- Continuously reorganized in response to
cell shape alteration, cell division and
environmental changes - Aids cell motility (e.g. sperm cells)
- Controls organelle location and transport of
molecules between them - Directs chromosome segregation during
mitosis
What are the different protein composition of the 3 types of cytoskeleton ?
- IFs – Fibrous proteins
- Microtubules – Globular tubulin subunits
- Actin – Globular actin subunits
What are Intermediate filaments basic properties ?
Keratin and Vimentin
- Ropelike fibers
- “Intermediate” diameter of - Composed of fibrous proteins
- Very flexible
- Provide tensile strength
- Protect cells against mechanical
stress (stretching)
What are some more basic properties of intermediate filaments ?
- Toughest and most durable cytoskeletal component - Survive concentrated salt solutions and nonionic detergents - Extend across cytoplasm and beyond cell periphery - Anchored to plasma membrane at cell to cell junctions (desmosomes) - Found in nucleus (lamina)
What is the structure of the intermediate filaments ?
- Dimers anti-parallel so ends are the same (no structural polarity) and filaments
associate by noncovalent bonding alone - Combined strength of overlapping tetramers along protein provides overall tensile
strength - Central domains homogenous (tight packing), end domains heterogenous
(interaction specificity in cytoplasm)
What is the function of intermediate filaments ?
- Prominent in cells subject to mechanic stress e.g. muscles, nerve cell axons, skin etc - Spread locally applied forces to prevent tearing and rupturing
How any of the intermediates are cytoplasmic and nuclear?
There are 4 major types
- 3 cytoplasmic and 1 nuclear
Explain intermediate filaments in Keratins ?
- Largest and most diverse group
- Further subdivided into acidic and basic keratins
- Composed of keratin filament subunit mixtures
- Span entire cell diameter, ends anchor to desmosomes on plasma membrane and indirectly connect with IFs on neighbouring cells
- Also specialised keratin in hair, teeth and nails/claws
Diseases of keratins - epidermolysis bullosa simplex (EBS)
- Rare inherited human genetic disease (1-3/million births)
- Caused by mutation in keratin gene (K5 or 14 commonly) – produces truncated keratin proteins which fail to assemble correctly into filaments in the epidermis
- Skin highly sensitive to mechanical stress – blistering, bruising, bleeding, scarring
- No cure – lifestyle management, pain management, antiseptic washes
Explain Intermediate filaments for Nuclear Lamina?
- Form 2D meshwork structure on inside layer
of nuclear envelope - Constructed from lamin filaments
- Disassembles and reforms during cell division
allowing chromosomal duplication - Lamin degradation controlled by
phosphorylation
What is a disease of lamins? and explain ?
Progeria
- Rare human genetic diseases (4-8/million births)
- Caused by mutation in lamin A gene – nucleus unstable and
misformed
- Children age prematurely (10 years per year)
- No cure – survival rare beyond 40’s
What are the basic properties of Microtubules ?
- Stiff hollow tubes
- Radiate from centrosome
- Rapid assemble/disassembly
- Key organisers in the cell
- Form mitotic spindle in mitosis
- Power mechanical beat of cilia and
flagella - Transport of vesicles, organelles and
macromolecules
What is the structure of Microtubules ?
- Composed of globular tubulin subunits
- a-tubulin and b-tubulin dimers form by
non-covalent bonding - Dimers stack to form wall of hollow
cylindrical tube - 13 parallel protofilaments with
alternating tubulin forms - Structural polarity provided by
asymmetrical ends - a-tubulin = -ve end
- b-tubulin = +ve end
What is the relation of centrosomes to microtubules?
- MTs extend from organizing structures
called centrosomes - Control location, number and orientation of
microtubules - Consist of paired centrioles orientated
perpendicular to each other - Hundreds of ring-like structures consisting
of g-tubulin – serve as start point
(nucleation site) for new MT
Explain the dynamic instability of microtubules ?
- Following nucleation MTs radiate out rapidly in minutes by addition of
a/b-tubulin dimers to +ve end - Can suddenly shrink or disappear through loss of dimers at free +ve
end - could regrow after shrinking, or start a new MT growth from a gtubulin ring - Process of rapid polymerisation and depolymerisation known as
dynamic instability
+ve ends protected from depolymerisation through ?
Binding specific
proteins – can bias location of stable MT formation
Dynamic instability driven by?
Intrinsic capacity of
tubulin dimers to hydrolyse GTP
Free tubulin dimers contain?
One molecule of
GTP bound to β-tubulin
GTP hydrolyzed to GDP upon?
Addition of dimer
to growing MT
During rapid polymerization, dimers link faster
than?
The rate of GTP hydrolysis
End of growing MT formed entirely of ?
GTPtubulin which forms “GTP-cap”
GTP-dimers associate more strongly and tightly
than ?
GDP-dimers – promotes polymerisation
Drugs can inhibit both ?
MT assembly
Colchicine) and disassembly (Taxol
Dynamic instability increases for ?
Mitotic spindle formation
During differentiation MTs ?
Stabilised more readily
Motor proteins transport?
Macromolecules/organelles using MT ‘tracks’ using
small, awkward, jerky steps
What is this powered by ?
Powered by repeat cycles of ATP hydrolysis
Kinesins direct traffic toward?
+ve end
Dyneins direct traffic toward?
–ve end
MTs organize and maintain the ?
Position of organelles in the cell
Kinesins help stretch ?
ER out like a tent across the cell
Dyneins pull ?
Golgi in close towards the nucleus (except in secreting cells!)
Spatial arrangement maintained ?
During cell growth (drugs can interfere)
MTs in cilia and flagella slightly different ?
To cytoplasmic MTs
