Cytoskeleton I Flashcards
Establishes cellular polarity
Cytoskeleton
Performs directional migration
Cytoskeleton
Responsible for the formation of the bipolar mitotic/meiotic spindle
Cytoskeleton
What are four major roles of the cytoskeleton?
- ) Establishes cell polarity
- ) Directional migration
- ) formation of mitotic/meiotic spindle
- ) Chromosome segregation
Also responsible for cytokinesis, intracellular transport, exocytosis, and endocytosis
Cytoskeleton
What are the three cytoskeletal components?
-have different distributions in the cell
Actin, Intermediate filaments, Microtubules
Cytoskeletal components have different distributions, this is important for cell
Shape & polarity, and tissue formation
Side that is towards the lumen
Apical face
Side that is towards the basement membrane
Basal face
Are assembled from smaller protein subunits
- Non-covalent polymers
- Dynamic
Cytoskeletal structures
Intermediate in size between actin filaments and microtubules
-more stable-the “tendons” of the cell
Intermediate filaments
Major components of the cytoskeleton and nuclear boundary and functional organization of cellular architecture
Intermediate filaments
Intermediate filaments provide protection from
Mechanical stress
Viscoelastic filaments within cells and at junctions between cells
-Stress absorbers
Intermediate filaments
Intermediate filaments have a role in signaling and controlling gene regulatory
Networks
Do intermediate filaments have any known associated motors?
No
Surround the nucleus, extend to cell periphery, and at cell-cell and cell-ECM junctions
Intermediate filaments
Intermediate filaments are dynamic. They are controlled by
Phosphorylation
What are four main functions of intermediate filaments?
- ) Mechanical support
- ) Cytoarchitecture
- ) Cell migration and movement
- ) Signal modulation
Large family of proteins (~70 genes) including keratins, neurofilaments, nuclear lamins among others. Many disease-assoc. mutations.
Intermediate filaments
What is the basic structure of an intermediate filament?
Two chained coil that assembles to form tetramer
The N-terminal and C-terminal ends of intermediate filaments are globular, and their coiled coil region is interupted by
Linker domains
Intermediate filaments assemble as antiparallel tetramers. In contrast to actin filaments and microtubules, the overall structure is
Not polar
Mutations in lamins cause
Laminopathies
Mutations in keratins cause
Skin blistering diseases
Actin filaments (F-actin) are polymers of the
globular protein, actin (G-actin), that contains a
bound
Nucleotide (ATP or ADP)
Are actin filaments polar?
Yes
In an actin filament, what is the
- ) fast growing end?
- ) slow growing end?
- ) “plus” or barbed end
2. ) “minus” or pointed end
The overall shape of the actin filament is
Helical
Modify the actin filament dynamics and higher order assemblies
Actin binding proteins
Both assembled from globular proteins by a condensation-polymerization mechanism to form a polar structure
Microtubules and actin filaments
The preferred end of monomer addition to actin and microtubules is the
Plus end
What do microtubules and actin filaments have at the growing end?
ATP or GTP cap
Is energy required for polymerization of actin filaments or microtubules?
No
Given all their similarities, are actin filaments and microtubules related?
No
The rate limiting step of elongating the barbed or “plus end of actin filaments or microtubules is
Nucleation
Preferentially added to the barbed (+) end of actin filaments
ATP-actin
ATP hydrolysis is not required for polymerization, but the bound nucleotide influences stability of the ends and interactions with other
Proteins
Most of an actin filament is made up of ADP-actin, with the exception of the extreme
Barbed end
In actin filaments and microtubules, hydrolysis of NTP to NDP takes place after
Polymerization
Soluble actin or microtuble subunits are in the
T form
Actin filament and microtubule polymers are a mixture of
-(-) end grows so slow that hydrolysis catches up
T (NTP) and D (NDP) form
Affect microtubule growth and stability
Nucleotide at (+) end
Stabilizes the (+) growing end of the microtubule
GTP-tubulin cap
Destabilizes the microtubule resulting in rapid depolymerization
GDP-tubulin subunits at (+) end
Lengthen or shorten as a function of time
-Catastrophe happens before rapid shortening
Individual microtubules
Determine the state of actin and its dynamics
Actin binding proteins
Actin binding proteins are targets of
Cell signaling cascades
A monomer or filamentous poymer
-a building block
Actin
Exist as singular units or are assembled into different structures by actin binding proteins
Filaments
Actin filaments are dynamic and are ultimate targets in
Cell signaling pathways
Important in vesicular and organelle transport
Tubulin and microtubules
Form the mitotic spindle, cilia and flagella, centriole, and basal bodies
Microtubules
Many cilia are motile, but most cells have a non-motile
-usually one per cell
Primary Cilium
Central in developmental signaling pathways
-sensory organelles
Primary Cilium
The only difference between the structure of motile cilia and the primary cilia is the primary cilum has no
Microtubule in the center
The microtubule organizing center
-forms poles of mitotic spindle
Centrosome
A consequence of the centrosome is that the (+) end of microtubules is located towards the
Cell periphery
The centrosome is organized around a pair of
Centrioles
Centrioles are surrounded by
Pericentriolar material
Centrioles duplicate beginning in
S phase of mitosis
Regulate state of microtubule assembly and stabilize or destabilize plus or minus end
Microtubule associated proteins (MAPs)
Bind to the side of microtubules and stabilize by side binding or bundle formation
MAPs
Can also sever microtubules
MAPs
An example of a MAP that acts in Alzheimer’s disease in neurofibrillary tangles
-connets microtubules
Tau
In order for the (+) end to reach the cell periphery, (+) tip proteins must inhibit
Catastrophes
Bind to and track with the + end of a
growing microtubule
(+) tip proteins
(+) end reaching the cell periphery allows for communication and connection with the cell cortex and interaction with the
Actin cytoskeleton
Capture chromosomes during mitosis
-Associated with kinetochore
(+) end
Can alter microtubule or actin polymerization
Natural toxins
Binds and stabilizes actin filaments
-found in death angel mushroom
Phalloidin
Depolimerizes microtubules
-From the autumn cross
Colchicine
Binds and stabilizes microtubules
- from pacific yew tree
- widely used as anti-cancer drug
Taxol
Widespread: seen during development, in chemotaxis, in tissue formation and repair, and in cancer metastasis
Cell migration
Migration of neutrophils to infection sites
Chemotaxis
What are the two ways to drive cellular movement?
- ) motor driven
2. ) polymerization driven
Can also be motor driven or polymerization driven
Intracellular transport
Can usurp the cellular machinery
Pathogens
An example of cellular motility is when a neutrophil chases a
Bacterium
Found in the blood and protect the body from bacteria that enter through the skin
Neutrophils
Neutrophils cahse bacteria by
Chemotaxis
Mechanisms that involve actin polymerization at the leading edge and myosin dependent contractions of the tail
Chemotaxis
Can drive cell migration by itself
Actin polymerization
Can commandeer the cell’s actin polymerization machinery during infection
Certain bacteria
How does actin polymerization alone provide the force for movement?
Elongation at the (+) end pushes against the membrane
More actin filaments are nucleated, existing filaments are severed to create more barbed ends, and branches are formed in existing filaments to generate the
Actin polymerization required for movement
Nucleates filaments from the sides of actin filaments,
making complex branched structures
-a complex of 7 proteins
Arp2/3
What activates Arp2/3 to enable it to nucleate actin filaments?
Rho-dependent signaling cascade
Dendritic (branched) actin filaments drive
Membrane protrusion
Involved in neutrophil migration, wound healing, invasion of metastatic cancer cells, and clathrin-dependent endocytosis
Arp2/3-dependent polymerization
Food born bacterium that infects intestinal epithelium and activates Arp2/3, which propels bacterium through cytoplasm
Listeria
Contain ƴ-tubulin ring complex that nucleates the 13
protofilaments of microtubules and caps the - ends
Centrioles
WASP/Scar binds to Arp2/3 complex and activates it. The complex then binds to existing filaments and makes a
-generates actin-polymerized movement
New filament growing out (branch)