Cytoskeleton Flashcards
Cytoskeleton definition
System of protein polymers that provide for the architecture, shape, motility of cells and for the directed movement of organelles and molecules within the cell
Components of cytoskeleton
Microtubules, microfilaments (actin filaments), intermediate filaments
Microtubules are polymers of ______, which is a ____ase
Tubulin dimers, GTP
MAPs do what ?
Stabilize and space Microtubule polymers and regulate interactions between cytoskeletal elements
MT - dynamic or no?
Highly dynamic, undergo rapid bouts of assembly and disassembly
MTs are polarized, Which end of the MT is dynamic?
PLUS END
Functions of MT
Make up mitotic spindle
Provide railways for organelle transport in most interphase cells
Key determinant of cell shape
Important in neurons for cell shape and axonal transport
Provide the backbone for cilia and flagella
Which cytoskeleton aspect is important for neurons?
MT, cell shape and axonal transport
Which cytoskeletal element is the backbone for cilia and flagella?
MT
What is a protofilament?
Stacks of tubulin dimers
Around how many protofilaments make up a MT
13
The catastrophe phase of MT dynamics refers to ?
Depolymerization
The catastrophe phase of MT dynamics refers to ?
Depolymerization
The rescue phase of MT dynamics refers to ?
Polymerization phase
Tubulin is a ____ase
GTP
The GTP cap exists on MT during which phase?
Polymerization phase
Tubulin dimers must be loaded with _____ for polymerization to happen
GTP
A regular MT polymer not going thru polymerization is ____ loaded
GDP
What is dynein? Which end of polymer is it directed to?
Microtubule associated motor protein, NEG end
What is Kinesin? Which end of polymer is it directed to?
Microtubule associated motor protein, POS end
The head domain of MAMPs is bound to ____
Microtubules, they STEP
Function of light / light&intermediate chains
Decided the cargo that motor proteins will carry, regulate the motor proteins and speed it travels
Functions of MAPs (non motor) and examples
Organize MTs, regulate MT stability, regulate MT dynamics
Tau, MAP1A etc
Nucleation of MTs occurs at the ______
Centrosome
The centrosome is located
Near the nucleus
Nucleation =
Genesis of a cytoskeletal polymer
Centrosome structure
2 centrioles
Gamma tubulin on - end of MT
Where are cilia located
Lung epithelium, trachea, fallopian tubes
MTs are important in sperm because
They allow sperm to move (tail)
Function of cilia
Move mucus / other substances
What is the basal body
Microtubule organizing center for cilia and flagella
Where are cilia Nucleated
At the basal body, under the membrane
What is the axoneme
9+2 MT structure of cilia and flagella
What connects the outer doublets to the inner doublet in cilia/flagella
Dynein
What is the purpose of dynein in cilia and flagella
Connects doublets to center, allows Microtubules to move in relation to each other (AKA bending)
Immotile cilia syndrome
Body wide defect in axonemal structure that result in obstructive lung disease and sterilization in males
(Can’t move mucus or repel sperm)
Kartagener’s syndrome
Combination of situs in versus (reversal of normal body asymmetry) and immotile cilia syndrome
Cilia not functional during early development = cells move to wrong spots and develop organs there
How are MTs related to cancer?
Cell division is reliant on MTs, if you mess with cell replication, cancer can result
How do neurotopic viruses exploit MTs?
Example?
Vectors bind to motor proteins and get transported all around cell; leads to gene expression of the virus in those cells
Herpes virus
How is lissencephaly related to MTs?
Mutations in LIS1 and double cortin
(Smooth brain)
How are MTs related to Charcot-Marie-tooth disease type 2A?
Mutation in specific kinesin
How are neurodegenerative diseases related to MTs?
Abnormalities/ mutations in tau, dynein, kinesis, spastin
What is the smallest of the cytoskeletal elements?
Microfilaments (actin filaments)
Structure of microfilaments
Helical (two chains wrapped around each other)
Non hollow
Microfilaments are polymers of ___
Actin
Are microfilaments dynamic or no
Highly dynamic if not stabilized
Actin is a ____ase
ATP
Where are microfilaments nucleated
Anywhere in the cell!
What motor proteins use microfilaments as a substrate
Myosin family of motor proteins
Polarized structure of microfilaments has what ends
Barbed (+) and pointed (-)
What end of microfilaments is favored for assembly
Barbed end
Most myosins moved towards the ___ end on microfilaments
Barbed
Functions of microfilaments
Concentrated in cell cortex for various functions
Cleavage furrow for pinching off cells in final stages of mitosis
Cell motility
Short range organelle transport (via myosin mp)
Contractility (muscle and non muscle)
Actin has ___ isoforms, what are they ?
3, alpha, gamma, beta
Which actin isoforms are found in most cells? Which is specific and for what?
Beta and gamma, alpha is specialized for muscle
What accessory protein is often bound to the structure of actin filaments
Tropomyosin (rope around)
Actin must be ____ loaded for Nucleation and polymerization
ATP
What does the NPF do in actin filaments Nucleation
Creates the ARP2/3 complex by grabbing actin molecules
Complex first binds to the side of an existing actin filament, then Nucleates a new filament off of other side
ALLOWS FOR BRANCHING AND NETWORKS
What is a spire
Actin filaments with accessory protein bound (like a string to help Nucleation
What are forming
Actin filaments with accessory protein bound (like a ring around filament) to help Nucleation
Actual actin filaments exist with actin bound to
ADP
Monomer sequestering meaning (AF)
Monomer bound to depolymerizing proteins, can’t be used until protein comes off
Capping meaning (AF)
Cap placed on barbed end, stops polymerization to make short capped filaments
Crosslinking meaning (AF)
Happens with short capped filaments or long filaments, creates bundles or networks that have structural functions and other functions within cytoplasm
Annealing meaning (AF)
Joining short uncapped filaments into long filament
What is made of F actin
Stress fibers, leading edge mesh works
What are stress fibers made of and what is their purpose
Myosin, a-actin in, formins (help Nucleation)
Basically the muscle for the cells
Contractibility
What are leading edge mesh works made of and what is their purpose
Arp2/3 (branching) , profilin, cofilin, etc
Can change shape of cell
What is a sarcomere made up of
Actin filaments that overlap with their pointed ends on the outside and barbed ends on the inside
What is the purpose of F-actin associated force
Generating mechanoenzymes with roles in contractility and intracellular transport
Allows sarcomeres to contract
Myosin 1 and myosin 5 have what light chains? What do they bind to ?
Calmodulin -binds to Ca2+ to control activity
Myosin 2 has ___ types of light chains ? What are they
Regulatory and essential
Regulatory light chains on myosin 2 are regulated by ___
Kinases
Essential light chains on myosin 2 regulate by
Binding to myosin - function like an off/on switch
Functions /structure of actin during cytokinesis
Ring of actin and myosin binds; contracts and pinches off cells
Myosin 2 & F actin in ring
Myosin 1 at poles
What forms of myosin and actin are present in the cleavage furrow
Myosin 2 and F actin
Microvilli are ____ based epithelial projections
They are located where in the body?
Actin
Small intestine ( 4 absorption during digestions)
What structure functions in the ear cells to detect sound waves ? What are they made of
Stereocilia, actin filaments
The _____ end of the actin filaments are located at the tip of the microvilli
Barbed
The ______ domain of lateral arms binds to membrane in microvilli
What is this made of ?
Hydrophobic
Myosin 1 (monomeric) & calmodulin
What is the purpose of the lateral arms in microvilli
Attach to actin filaments that make up structure, stabilizes filaments by binding to the membrane
What stabilizes the array of microfilaments in the microvilli
Villin and fimbrin
The physical link between the cytoskeleton and the extracellular environment provides ___
Mechanical continuity
Erythrocyte (RBC) cytoskeleton is made up of
Spectrum tetramers (strings) and f-actin (scaffold) to form the spectrin web
The actin serves as nodes ; makes shape
Hereditary spherocytosis
Deforms red blood cells to fragile spherocytes because of weakened binding affinity of spectrin to band 4.1
Hereditary elliptocytosis
Deforms red cells to fragile elliptocytes because of incomplete formation of spectrin
Breast cancer related to actin
In some forms of actin associated protein Tensin (links integrity receptors to the actin cytoskeleton, is disrupted promoting metastatic migration of cancerous cells
Familial hypertrophic cardiomyopathy
Mutations in a specific cardiac actin
Only myocardium impacted
Mutations in skeletal muscle actin are associated with ____ characterized by _______ abnormalities of the muscle and variable degrees of muscle _____
Congenital myopathies, structural, weakness
Mutations in VI cause
Deafness; prevent proper formation of stereocilia
Mutations in myosin VII associated with
Deafness, neurological disorder, and blindness (Usher syndrome type 1)
How do bacterial pathogens use cytoskeletal elements
Bacterium moves by developing actin-Nucleation-like proteins to push around bacterium
Phalloidin causes cells to ____ by
Die, binding and stabilizing actin filaments
Cells will die because actin dynamics=0
Intermediate filaments are dynamic or no
Not dynamic, don’t have a polarized side
Functions of intermediate filaments
Space filling elements (increases cell volume)
Give cells tensile strength (structural stability)
Specialized functions depending on cell type
Important at cell junctions
Intermediate filaments are much ___ conserved across cell types than Microtubules or microfilaments
Less
What cytoskeletal elements can be used as cell specific markers
Intermediate filaments
Intermediate filament formation
Helical string with (NH2 end and COOH end)
Coiled dimer
Two coiled dimers together (protofilament) (lego brick)
Stacks like legos
Keratins are which type of cytoskeletal element
Where are they found
Intermediate filaments
Epithelial cells and epidermal derivatives
Nuclear lamins are what type of cytoskeletal elements
Where are they found
Intermediate filaments
In the nuclei of every cell
Epidermolysis bullnose simplex
Mutation in keratin genes expressed in basal cell layer of epidermis, result in a skin that is very sensitive to mechanical injury
*dangerous because it opens skin to infection
Progeria
Fast aging disease associated with mutation in nuclear lamin protein
Intermediate filaments differ in different cells means that disease …..
Specific diseases are associated with specific problems
Keratins are mutated in more than ____ diseases
20
Desmin is mutated in
Cardiomyopathies
Neurofilament proteins are mutated in
(Small subunit mutated in the IF/2E forms of Charcot-Marie tooth disease
Peripherin is induced after
Peripheral nerve industry
Glial fibrillation acidic proteins are mutated in
Alexander disease (a leukodystrophy, which results in abnormal myelin)
