Module 6: The Cytoskeleton (Intermediate Filaments and Septins, Cell Polarization and Migration) Flashcards
- forms cytoplasmic filaments.
- have cells that are subject to mechanical stress.
- not found in animals with rigid exoskeletons
intermediate filaments
Types of intermediate filament (4)
- Nuclear
- Vimentin-like
- Epithelial
- Axonal
- The central domain of elongated proteins in intermediate filaments is a conserved __ containing 40 or so __ that forms an extended coiled-coil structure.
- a pair of __ then associates in an antiparallel fashion to form a __.
intermediate filament construction
- α-helical domain
- heptad repeat motifs
- parallel dimers
- staggered tetramer
Do intermediate filaments contain a binding site for nucleotides?
No
Are the two ends of an intermediate filament the same or different?
Same
They pack together laterally to form the filament, which includes eight parallel protofilaments made up of tetramers.
intermediate filament construction
tetramers
How many individual α-helical coils are present in a cross-section of the filament?
intermediate filaments
32
The mechanical properties of intermediate filaments: They have a __ character, are easily __, but are extremely difficult to __and can be __.
intermediate filaments
- ropelike
- bent
- break
- stretched
Which is the most diverse intermediate filament family?
Keratins
Made up of equal mixture of type I (acidic) and type II (neutral/basic) keratin proteins, forming a heterodimer.
intermediate filaments
Keratin filament
each
- What holds cross-linked keratin networks together?
- What happens to cross-linked keratin networks after cell death?
intermediate filaments
- Disulfide bonds
- Survive
Keratins are used in the diagnosis of __(__).
intermediate filaments
epithelial cancers (carcinomas)
A single epithelial cell produces __ types of keratins, they __ into a __ network.
intermediate filaments
- multiple
- copolymerize
- single
What structure is involved in cell-cell contact?
intermediate filaments
desmosomes
What structure is involved in cell-matrix contact?
intermediate filaments
Hemidesmosomes
- defective keratins in the basal cell layer of the epidermis.
- causes skin blisters in response to even very slight mechanical stress, which ruptures the basal cells.
- mouth, esophageal lining, and cornea of the eye can be affected
- Cell rupture as a consequence of mechanical trauma and a disorganization or clumping of the keratin filament cytoskeleton.
intermediate filaments; a condition
epidermolysis bullosa complex
- found in high concentrations along axons
- have subunits NF-L, NF-M, and NF-H, assemble in vivo into heteropolymers.
intermediate filaments
neurofilament
in vivo-performed or taking place in a living organism.
- During axonal growth, new neurofilament subunits are incorporated all along the axon in a dynamic process that involves the __ of subunits along the filament length as well as the ends.
- The level of __ controls axonal diameter during axonal growth.
- addition
- neurofilament gene expression
What disease is associated with neurofilaments?
Amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s disease)
sclerosis- areas of scar-like tissue (also called plaques or lesions)
- A vimentin-like filaments expressed in skeletal, cardiac, and smooth muscle, where it forms a scaffold around the Z disc of the sarcomere.
- It stabilizes muscle fibers.
intermediate filaments
desmin
They exhibit muscle-cell abnormalities such as misaligned muscle fibers. They lack desmin.
intermediate filaments; what animal?
mice
What human conditions are associated with defective desmin? (2)
- Muscular dystrophy
- cardiac myopathy
MD- progressive weakness and degeneration of skeletal muscles
Scaffold proteins that control myriad cellular processes including, transcription, chromatin organization, and signal transduction.
intermediate filaments
A-type lamins
Tissue-specific diseases associated with mutant versions of lamin A.
laminopathies
- intermediate filament network linked to the rest of the cytoskeleton
- members of a family of proteins
- They are large and modular, containing multiple domains that connect cytoskeletal filaments to each other and to junctional complexes.
Plakins
Interacts with protein complexes that connect the cytoskeleton to the nuclear interior.
intermediate filaments
Plectin
- an additional filament system that forms ring and cagelike structures.
- act as scaffolds to compartmentalize membranes into distinct domains.
- recruit and organize the actin and microtubule cytoskeleton.
Septins
- form a neck between a dividing yeast mother cell and its growing bud.
- recruit the actin-myosin machinery necessary for cytokinesis.
- involved in cell division, migration, vesicle trafficking, and act as a diffusion barrier.
Septins
How many septin genes are present in humans?
13
- relies on the coordinated deployment of components and processes.
- involves the dynamic assembly and disassembly of cytoskeletal polymers.
- structure of cytoskeletal polymers is through regulation and modification of their structure.
- action of motor proteins moving along cytoskeletal polymers or exert tension against them.
cell migration
How do cells move? Which cells do this to search for food? Which cell is an exception? (3)
cell migration
- by crawling
- Amoebae
- Sperm
unicellular, can alter its shape( extending and retracting pseudopods)
Structure of an animal is created through the __ of individual cells to specific target locations.
migrations
Which cells crawl during nervous system construction?
Neural crest cells
Which cells crawl to sites of infection to engulf foreign invaders? (2)
- macrophages
- neutrophil
Which cells crawl for bone remodeling and renewal?
Osteoclasts
Which cells migrate through connective tissues?
Fibroblasts
What is a pathological example of cell crawling?
Cancer cells
Steps in cellular migration (3)
- protrusion
- attachment
- traction
The plasma membrane is pushed out at the front of the cell.
a step in cell migration
protrusion
Protrude - to stick out
The actin cytoskeleton connects across the plasma membrane to the substratum.
a step in cell migration
attachment
The bulk of the trailing cytoplasm is drawn forward.
a step in cell migration
traction
pulling something over a surface
What generates the forces required for protrusion?
cell migration
actin polymerization
What do protrusive structures contain?
cell migration
Dense cores of filamentous actin
Give 5 protrusive structures/protrusions (5)
cell migration
- filopodia
- lamellipodia
- invadopodia
- podosomes
- blebbing
One-dimensional protrusions formed by migrating growth cones of neurons and some types of fibroblast, containing a core of long, bundled actin filaments.
filopodia
Two-dimensional sheetlike structures formed by epithelial cells and fibroblasts, containing a cross-linked mesh of actin filaments.
lamellipodia
Three-dimensional actin-rich protrusions important for cells to cross tissue barriers. (2)
- invadopodia
- podosomes
A protrusion that depends on hydrostatic pressure within the cell, generated by the contraction of actin and myosin.
Blebbing
- Epithelial cells of the epidermis in fish and frogs that are rich in keratin filaments.
- They function form an epithelial sheet that covers the animal and specialize in closing wounds.
- It has a large lamellipodium and a small trailing cell body that is not attached to the substratum.
keratocyte
While the lamellipodia crawl forward, the __ remain stationary with respect to the __.
- actin filaments
- substratum
Orientation of actin filaments in the lamellipodia: The __ ends face forward, and the __ ends are attached to the sides of other actin filaments by __.
- plus
- minus
- Arp2/3 complexes
The two-dimensional actin web in lamellipodia is formed by cross-linking __ through __.
- actin filaments
- Arp2/3 complexes
refers to the process where actin filaments assemble at the front of the lamellipodium and disassemble at the back, maintaining dynamic turnover.
Actin Filament Dynamics in Lamellipodia
Treadmilling
- Where is actin filament nucleation localized in lamellipodia?
- Where does filament depolymerization occur in lamellipodia?
- At the leading edge
- behind the leading edge
- binds preferentially to actin filaments containing ADP-actin.
- New T-form filaments are resistant to depolymerization because this efficiently disassembles older filaments but does not act on the new T-form filaments at the leading edge.
- maintains actin turnover in lamellipodia.
Actin Filament Dynamics in Lamellipodia
Cofilin
- For the leading edge of a migrating cell to advance, __ of the membrane must be followed by __ to the __ at the front.
- For the cell body to follow, __ must be coupled with de-adhesion at the rear of the cell.
Actin Filament Dynamics in Lamellipodia
- protrusion
- adhesion
- substratum
- contraction
What mediates the connection between the actin cytoskeleton and the substratum?
Actin Filament Dynamics in Lamellipodia
Integrin-mediated adhesions.
Dynamic assemblies of structural and signaling proteins that connect the actin cytoskeleton to the substratum.
Actin Filament Dynamics in Lamellipodia
focal adhesions
Forms bipolar filaments that associate with actin filaments at the rear of the lamellipodium, pulling them into a new orientation.
Cell migration
Myosin II
Which cytoskeletal processes are essential for cell migration? (3)
- Actin polymerization
- dynamic adhesions
- myosin contraction
Disengaged interaction between actin network and focal adhesions, polymerization pressure at the leading edge, and myosin-dependent contraction cause the actin network to slip back.
Retrograde flow
The front end of the cell remains structurally and functionally distinct from the back end.
Cell migration
What is required for oriented cell divisions in tissues and for the formation of a coherent, organized multicellular structure?
cell migration
Cell polarization processes
Cytoskeletal coordination manifests during cell migration through the establishment of __.
cell polarity
Establishment of cell polarity depends on the local regulation of the __ by __ signals.
- actin cytoskeleton
- external
Which monomeric GTPases are members of the Rho protein family? (3)
- Cdc42
- Rac
- Rho
involved in bundling actin filaments with myosin II filaments into stress fibers and clustering integrins and associated proteins to form focal adhesions.
actin cytoskeleton regulation
Rho
Promotes actin polymerization and bundling to form filopodia at the plasma membrane.
actin structure; actin cytoskeleton regulation
Rho-Cdc42
Actin polymerization at the cell periphery and the formation of sheetlike lamellipodial extensions.
actin dynamics; actin cytoskeleton regulation; what facilitates these?
Rac
What proteins are activated by Cdc42 and are associated with the Wiskott-Aldrich Syndrome?
WASp proteins
A severe form of immunodeficiency in which immune system cells have abnormal actin-based motility and platelets do not form normally.
Wiskott-Aldrich Syndrome
- activates WASp family members
- activates the cross-linking activity of the gel-forming protein filamin
- It inhibits the contractile activity of myosin II.
- It stabilizes lamellipodia and inhibits the formation of contractile stress fibers.
Rac-GTP
- turns on formin proteins to construct parallel actin bundles
- activates a protein kinase that in indirectly inhibits the activity of cofilin, leading to actin filament stabilization
- inhibits a phosphatase acting on myosin light chains
Rho-GTP
What does Rho-GTP activate to construct parallel actin bundles?
Formin proteins
The movement of a cell toward or away from a source of some diffusible chemical.
chemotaxis
How do cells set up large-scale cell polarity in chemotaxis?
what molecule is used? Throug…
Through Rho family proteins
Which cells are known to move toward a source of bacterial infection?
Neutrophils
Neutrophils ability to detect very low concentrations of __ derived from __ enables them to detect bacterial infections.
- N-formylated peptides
- bacterial proteins
When a chemoattractant binds to its __, it activates __, leading to the production of [PI(3,4,5)P3], which activates __ and subsequently __, resulting in __.
Neutrophil polarization and chemotaxis
- GPCR
- PI3Ks
- Rac GTPase
- Arp 2/3
- lamellipodial protrusion
Binding of a chemoattractant activates __, which enhances myosin-based contractility
Neutrophil polarization and chemotaxis
Rho
Rac and Rho activation directly inhibit each other, such that Rac activation dominates in the __ of the cell and Rho activation dominates in the __.
- front
- rear
What is the result of the interactions between Rac and Rho activation?
Functional polarity in the cell