cytoskeleton I Flashcards
The cytoskeleton is a
dynamic intracellular structure (or set of structures) that serves to establish order within the cell as well as to organize the cells in their environment.
The cytoskeleton provides:
- Cell shape
- Mechanical strength
- The structures needed for locomotion
- Support for the plasma membrane
- The scaffold for the spatial organization of organelles
- The means for intracellular transport of organelles and other cargo.
The cytoskeleton is formed by
three different families of proteins that assemble to form large filamentous or tubular, non-covalent polymers, each with distinct mechanical properties, dynamics and functions.
The three types of cytoskeletal element are:
- microfilaments
- microtubules
- intermediate filaments.
Role of Nucleotide
GTP:
Microtibules:
favors microtublue growth
Accessory Proteins
Microtubules

Motor proteins:
- dyenins assembly/disassembly
- kinases
Assembly and disassemby
Accessory proteins of intermediate filaments
- assembly/dissasemby
- corss linking
- membrane anchor
Microtubule function
- movement of flagella and cilia
2. scaffold for cell organization and movement of organelles (including chromosomes)
intermediate filament function
mechanical stability
microtubule predominant protein:
tubulin a, B, y
intermediate filament predominant filament:
carious: vimentin, keratin, neurofilament proteins, GFAP
structure of microtubules
tubular
25 nm diameter
structure of intermediate filament
complex rope
10 nm diameter
By way of their architecture, microtubules have
α tubulin on one end and β tubulin on the other end. This confers polarity on the microtubule:
β tubulin =
α tubulin =
plus end
minus end
The GTP-bearing β subunits favor _____. In contrast, the α tubulin minus end tends to be _____
polymerization – the plus end is the end that grows
disassembling or shrinking.
As GTP-containing dimers become incorporated more deeply in to the MT,_____
GTP is hydrolyzed to GDP.
GDP weakens the
tubulin interaction in the protofilament
Treadmilling is
growth at the plus end, disassembly at the minus end
In response to a particular cellular activity, the plus end may lose its______.
This causes _______.
GTP-rich cap
rapid shrinkage from the plus end until GTP-containing dimers are added back
“dynamic instability” of the microtubule.
- MT capping proteins that bind to the ends of MTs usually increase their stability o MT severing proteins expose GDP-rich regions and thus promote MT instability
- Examples of severing proteins include Spastin and Katanin
Inhibitors of polymerization:
- Colchicine
- Vinblastine
- Vincristine
- Prevents microtubule growth – bad for the cell
Stabilizers of polymerization:
- Paclitaxel (Taxol)
- Causes tubule and tubulin aggregates
– bad for the cell
Molecular motors:
Proteins that can transform the energy of ATP hydrolysis into motion (or walking) along microtubules, using MTs as “tracks.”
There are two classes of molecular motor proteins:
- Kinesins: move cargo toward the plus-end
2. Dyneins: move cargo toward the minus-end
Kinesins:
move cargo toward the plus-end
Dyneins:
move cargo toward the minus-end
Molecular motors have two important domains:
- Cargo-binding domain
2. Motor domain (or “head region”) – hydrolyzes ATP and reversibly minds to microtubules
Mechanochemical Cycle of Motor Proteins
–Coordinated with ATP hydrolysis:
- MT binding
- Conformational change
- MT release
- Conformational relaxation o MT re-binding
This process moves the motor protein and the cargo along the microtubule in a stepwise fashion.
The mitotic spindle is constructed from :
MTs and associated proteins and serves to segregate the replicated chromosomes during mitosis.
Three types of MTs can be distinguished:
- Astral MTs:
- Kinetochore MTs:
- Overlap MTs:
Astral MTs:
radiate out from the centrosomes
Kinetochore MTs:
attached to the kinetochore formed at the centromere of each duplicated
chromosome
Overlap MTs:
interdigitate at the equator of the spindle
In all cases, microtubule plus-ends point
away from the centrosomes (or spindle poles).
Multimeric plus-end-directed, kinesin-like motor proteins bind to ____
and cause _____
This is enhanced by:
overlap MTs from opposite poles.
the spindle to grow and the centrosomes to become more distant.
pulling forces transmitted by astral MTs.
cilia compared to flagella:
Cilia are shorter than flagella and are found in large numbers on the apical surface of epithelial cells (for example, those of the respiratory tract).
The axoneme has a special structure called
a 9 + 2 array:
The axoneme is responsible for
ciliary beating and can bend because of the highly coordinated action action of dynein activity.
cilia function:
Beating with a whip-like motion in a staggered pattern, Cilia move fluids over the surfaces of cells
Non-motile primary cilia serve special sensory functions:
- Photoreceptors (outer segment)
- Chemosensors (for example: olfactory neurons)
- Mechanosensors
cilia in respiratory tract
In the respiratory tract, this action moves dust particles, bacteria, and mucus toward the mouth for elimination.
Primary cilia or monocilia
occur singly in a great variety of cells and may or may not be motile.
a 9 + 2 array:
- MTs and their associated proteins are arranged as a ring of 9 special doublets surrounding a pair of single microtubules
- Accessory proteins hold this array together o The axoneme is anchored in basal bodies
The motor action of dynein heads causes microtubules to
slide against one another. When this sliding is prevented by microtubule anchoring, as in the axoneme, bending results.
diseases of intermediate filaments:
- epidermolysis bullosa simplex (keratin)
- charcot marie tooth (neurofilament)
- ALS (neurofilaments)
- progeria (lamins)
epidermolysis bullosa simplex
- Keratin mutations may interfere with filament assembly.
2. The resulting epidermis is highly sensitive to mechanical stress and blisters easily
Charcot-Marie-Tooth Syndrome
Mutations in the light chain may interfere with axonal transport of neurofilament subunits and
peripheral neuropathy
Amyotrophic Lateral Sclerosis (ALS)
Abnormal neurofilament assembly seems to be involved in the neurodegenerative
disease
Progeria Syndroms
Mutations in lamins can result in nuclear instability
microtubule diseases
- primary ciliary dyskinesia syndrome (dynein)
2. peripheral neuropathy
peripheral neuropathy
- Mitosis serves as a major drug target.
- MT toxins block mitosis and, thus, are important therapeutic tools for cancer treatment.
- They may adversely affect other MT functions, such as
- axoplasmic transport
primary ciliary dyskinesia syndromes
- mutation in dynein motor
- Photoreceptor outer segments are modified monocilia
- That such cilia may operate as chemosensors
- -Anosmia - That establishment of left/right identity requires normal function of monocilia on nodal cells during gastrulation
Anosmia
probable explanation for cyst formation in developing kidney
Examples of cytoplasmic IFs:
1) Vimentins
2) Keratins,
3) Neurofilament proteins
4) Glial fibrillary acidic protein (GFAP)
Vimentins are present
in a majority of cell types.
Keratins:
a family of about 50 proteins, are dominant components of the epidermis and its appendages, providing mechanical strength.
Neurofilament proteins
co-assemble to form neurofilaments, which are found in high concentration in vertebrate axons. Neurofilament abundance appears to control axonal diameter.
Glial fibrillary acidic protein (GFAP) is the
IF protein characteristic of astrocytes in the CNS. Therefore, GFAP IFs are abundant in connection with inflammatory and/or degenerative processes in the brain. For example, Alzheimer plaques are surrounded by GFAP-rich reactive astrocytes.
