Cells 2 Flashcards
What are the components of cytoskeleton ?
- Actin filaments (microfilaments)
- actin
- 7nm diameter - Intermediate filaments
- 6 classes, numerous proteins
- 8-12 nm diameter - Microtubule
- tubulin
- 25 nm diameter
What are the functions of the cytoskeleton?
- structural support & stability
- organization
- cell division
- cell movement
- tracks for motor proteins to move organelles & vesicles within cells
Describe the structure of microtubules
- Non-branching, rigid, hollow tubes
- a and B tubulin protein subunits
Polar
- minus (-) end
- plus (+) end
What are the functions of microtubules ?
Intracellular transport
-movement of vesicles & organelles via motor proteins
Cell motility
- movement of cilia and flagella via motor proteins
- cell elongation and mivement
Mitotic spindle
-attachment of chromosomes & their movement during cell division
Rigid intracellular skeleton
-maintenance of cell shape & polarity
Assemble and disassemble as the needs of the cell change
Describe the structure of centrioles
9 Triplets of microtubules arranged around a central axis
-Each triplet consists of 1 complete and 2 incomplete microtubules fused
What are the functions of centrioles?
-Organize the centrosome
- Basal body formation
- provide basal bodies necessary for assembly of cilia and flagella
- Mitotic spindle formation
- formation of centrosome & alignment of the mitotic spindle during cell division
Explain the structure of the centrosome
Microtubule organizing center (MTOC)
Structure
- contains a pair of centrioles
- arranged such that one is perpendicular to the other
- amorphous protein matrix
- more than 200 proteins
- Gamma-tubulin ring complexes
- nucleation sites for microtubules
What is the function of the centrosome?
-Organize microtubules
- initiate microtubule formation
- Microtubules are nucleases at the centrosome at their negative(-) ends
- positive (+) ends point out and grow toward the cell periphery
What are the mitotic spindle poisons?
Colchicine
Taxol(palcitaxel)
What is colchicine?
Anti cancer compound
- prevents polymerization
- binds to unpolymerized tubulin molecules
- if given to dividing cells, mitotic spindle breaks down
- programmed cell death
Related compounds
- vinca alkaloids
- vinblastine
- vincristine
What is taxol (palcitaxel)?
Anti cancer compound
- stabilizes and prevents microtubule disassembly
- preferentially binds tubulin within associated microtubules
- Arrested dividing cells in mitosis
- unable to achieve metaphase spindle conformation
- programmed cell death
Describe microtubules
Polymerization
- organized & directed by microtubule organizing centers
- basal bodies
- centrosome
GTP dependent
Highly dynamic (mitotic spindle) or relatively stable (cilia)
- change in length
- fast growing at positive end, slow growth or disassembly at negative end
Describe microtubule associated proteins (MAPs)
Tau proteins
- abundant in neurons of the CNS
- stabilize axonal microtubules
- hyperphosphorylation of tau proteins can result in self-assembly of tangles
- linked to Ahlzeimer’s disease
Describe the Dynein family as microtubule motors
- move in the (-) direction along microtubules
- retrograde
2 members
- cytoplasmic dyneins
- axonal dynein
- located in cilia & flagella
Binding sites for vesicles, organelles or another microtubule
Largest & fastest of the known molecular motors
-dynein 14 um/sec vs kinesin 3 um/sec
Describe the kinesin family as a microtubule motors
- Move in the (+) direction along microtubules
- anterograde
- binding sites for vesicles, organelles, microtubules
- about 40 distinct kinesins humans
Explain the structure and function of the cilia & flagella
Motile structures
-highly specialized
- Microtubules and axonemal dynein motor proteins
- Characteristic arrangement found in almost all eukaryotic flagella and cilia
-Movement produced by the bending of the core (axoneme)
- Accessory proteins cross-link adjacent microtubules together
- As a result, dynein motors produce a bending movement
The cilia is anchored to the …
Basal body
-thin, dark staining band at base of cilia
What is the function of the cilia?
Move fluid and particles along epithelial surfaces
Describe the structure of the cilia
Microtubule-based, hair like structure
- motile - beat in synchronous pattern
9+2 microtubule arrangement
Pair of dynein arms
- motor protein - binds adjacent microtubule
Explain the primary cilia as a sensory antennae
Photoreceptors
-outer segment of rods derived from primarily cilia
Chemoreceptors
-odor detection by receptors on primarily cilia of olfactory neurons
Mechanoreceptors
- primarily cilia of epithelial cells monitors the flow of fluid through kidney tubules
- defects underlie a variety of disorders
- polycystic kidney disease
Briefly describe the structure of the primary cilia
- Microtubule based, antennae-like structure
- 9+0 arrangement
- Emanates from almost cells
- Anchored to cell via the basal body
- Develops from one centriole following cell division
Describe the structure of the intermediate filaments
Rope-like filaments
Structure: formed by non-polar & highly variable subunits
What are the functions of the intermediate filaments ?
Structural
- stabilize cell structure
- mechanical strength
- maintain the position of the nucleus and other organelles
- Resist shearing forces
- extend across cytoplasm
- connecting with desmosomes & hemidesmosomes
Essential for integrity of cell- cell & cell-ECM junctions
What are the classes of intermediate filaments?
- keratins
- vimentin & vimentin-like
- neurofilaments
- lamins
- beaded filaments
Explain keratins as intermediate filaments
Acid & basic cytokeratins
- diverse group
- over 50 isoforms
-found in all epithelial cells
explain vimentin & vimentin like as intermediate filaments
Diverse family
-most widely distributed in the body
Vimentin
-most abundant in mesoderm-derived cells
Vepimentin-like found in a variety cells
- Desmin: muscle cells
- Glial fibrillar acid protein (GFAP): glial cells & astrocytes
Explain neurofilaments as intermediate filaments
-Assembled from neurofilament proteins of different molecular weights
- Extend from cell body into the ends of axons & dendrites
- Provide structural support
-Found primarily in neurons
Explain the lamins as intermediate filaments
Found in nucleus of all nucleated cells
-nuclear lamina
Lamin A & B proteins
Explain beaded filaments as intermediate filaments
-Eye lens-specific group
Contrast the types of actin
G-actin= free actin molecules in cytoplasm
F-actin= polymerized actin in a filament, ATP dependent
Describe the structure if actin filaments
Made up of protein actin
Polarized structures
- fast growing (+) positive end
- slow growing (-) negative end
May exist as single filaments, in bundles, or in networks
What is the function of the actin filament?
Variety of cell functions
- anchorage
- structural core of microvilli & stereocilia
- cell motility
- locomotion
- extension of cell processes
What are the actin & fungal toxins?
Phalloidin & cytochalasins
What is phalloidin?
- toxin found in Amanita phalloides
- used in cytoskeleton research
- disrupts normal function of actin
- binds F-actin more tightly and G-actin
- promotes excessive polymerization and inhibits de polymerization
- inhibits cell movement
- disrupts normal function of actin
Other toxins (amatoxins) are responsible for the toxic effects following oral ingestion
-liver and kidney failure & death 4-8 days after consumption
What are cytochalasins?
- other fungal products
- block polymerization of actin
- Can be used to inhibit cell movement, division, & induce programmed cell death
Describe microvilli
- cylindrical, membrane bound cytoplasmic projections
- 1-3 um in length
- core of 25-30 actin microfilaments
- Cross linked by villain
- Anchored into the terminal web
Describe the structure of stereocilia
Unusually long microvilli
-up to 120 um in length
Actin filament bundle anchored to terminal web
Where can stereocilia be found?
Limited distribution
- Epidydmis
- proximal Ductus deferens
- sensory hair cells of inner ear
Describe myosin as an actin motor
Human genome includes about 40 different myosin genes
Myosin II
- Generates the force for skeketal muscle contraction
- formed from 2 heavy chains & 4 light chains
- tail-tail interactions result in formation of bipolar thick filaments
- several hundred myosin heads
Each head binds and hydrolyzes
What are the myosin structural changes for actin motors?
Stage 1: attachment- rigor conformation
Stage 2: release- ATP binds, reduces myosin affinity for actin
Stage 3: bending- ATP hydrolysis, cinfirmational change
Stage 4: force generation
- weak binding of myosin to actin causes release of inorganic phosphate
- release triggers tight binding & power stroke
- force-generating conformational change
Stage 5: reattachment
-rigor conformation
How is actin involved in cell movement?
- actin filaments mostly oriented with + end facing forward
- -ends frequently attached to the sides of other actin filaments via actin- related protein (ARP) complexes
Actin web as a whole undergoes treadmilling
- Assembling at the front
- Disassembling at the rear
ARP complex highly concentrated near front of lamellopodia where actin nucleation most active
- Actin filaments
- ARP complex
Dense actin filament mesh work at leading edge
How does actin help with plasma membrane protrusions?
Protrusions driven by actin
Different types of protrusion structures based on organization of actin
Filipodia
- Finger like projections
- Core of long, bundled actin filaments
Lamellipodia-fibroblasts
-Sheet-like structures
Pseudopodia- white blood cells
-3 dimensional projections
Explain the cell movement- lamellipodia
Common example- fibroblasts of connective tissue
Complex & integrated process
- Protrusion
- Actin polymerization at plus (+) end protrudes lamellipodium - Attachment
- Focal adhesions anchor the actin cytoskeleton to the extracellular matrix via integrins proteins
- Contraction
- Bulk of the training cell & cytoplasm is drawn forward
What is chemotaxis?
Movement within tissue along a chemotactic gradient towards the source of inflammation
- N-formylated peptides
- Peptides attached to extracellular matrix
Summarize neutrophil migration
Extravasion
- Rolling
- Activation
- Adhesion
- Transendothelial migration
Process of diapedisis
-Extension of a pseudopod between endothelial cells
-Pass the basement membrane into the tissue.
What are inclusions?
Cytoplasmic or nuclear structures formed from metabolic products of the cell
Pigments- membrane bound
Describe Lipofuscin as an inclusion
Brown-goldfish pigment
Generally seen in non-dividing cells
- Accumulating over years
- “wear and tear” pigment
-Accumulation of oxidized lipids, phospholipids, metals and other organic molecules as result of lysosomal digestion
Describe hemosiderin as an inclusion
- brown pigment
- Iron-storage complex found in cytoplasm
- Commonly found in macrophages
- Likely formed by indigestible residues of hemoglobin following phagocytosis of red blood cells
- Demonstrated in the spleen, liver, lung
Deposits may be also be linked to diseases of iron overload
Describe melanin as an inclusion
- Dark brown/brown/ reddish pigment produced by the oxidation of tyrosine
- Produced by melanocytes in the skin & responsible for color of skin/ hair pigmentation
- Also produced by certain neurons of the brain
Describe glycogen as an inclusion
- Non-membrane bound, TEM dense bodies
- single(beta) 20-30nm particles or rosettes (alpha)
- Storage form of glucose
- Catabolism releases glucose for energy
Describe lipids as an inclusion
-Non-membrane bound, TEM dense
- fat droplets
- spherical droplets of triglyceride
- Liquid at body temperature
-Energy store and source of short carbon chains for membrane synthesis
Lipid storage diseases (lipodoses)
-lipid droplets accumulate in abnormal amounts or locations
