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Cytoskeleton
exam 3
35
Medical
Graduate
09/22/2011

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Term
Fx of Cytoskeleton
Definition
  1. structural support to eukaryotic cells (against physiological strain)
  2. determine the shape of cells
  3. serves as intraccelular high way (transportation and movement)
  4. provides cell with the ability to form cell-cell and cell-extracellular matrix adherence.
  5. separate chromosomes and aids in cell division (cytokinesis),
  6.  prevent cells from being damaged by external force.

 

Term
Types of cytoskeletal filaments
Definition
  1. microtubules
  2. actin filaments or microfilaments
  3. intermediate filaments
Term
Microtubules
Definition
determine position of organelles and maintain cell shape (polarity); direct intracellular transport (vesicles and organelles);necessary for cell division, and moving of cilia and flagella.
Term
actin filaments or microfilaments
Definition
  1. determine shape of cell's surface.
  2. important for whole-cell locomotion (crawling)
  3. important for cytokinesis, exocytosis, endocytosis, and movement of membrane proteins.
Term
intermediate filament
Definition
  1. provide cell with mechanical strength
  2. provide cell with resistance to shear stress;prevent physical damage
Term
Fx of Cytoskeletal-associated accessory proteins
Definition
regulate spatial distribution and the dynamic behavior (i.e. assembly and disassembly) of cytoskeletal filament via binding either to the filaments or to the filament's free subunit in the cytosol.
Term
what are some cytoskeletal associated accessory protein?
Definition
  1. Nucleating protein: determine production/assemble site of new cytoskeletal filament.
  2. monomer-sequestering proteins: bind to monomer and keep it away from filament polymerization (inhibit).
  3. side-binding proteins (microtubule-associated proteins): stabilize or destabilize filaments by binding to their sides.
  4. capping (end blocking) proteins: bind to ends of filaments and affect their dynamics (assembling or disassembling)
  5. cross-linking proteins (bundling and gel-forming protein in actin filament): organize filament into larger structure, like a bundle.
  6. severing protein: break long filament into smaller filaments.
  7. motor protein: bind to a polarized cytoskeletal filament and use energy generated by ATPase to move steadily along it.
Term
Microtubule
Definition
  1. Location:origin> centrosomes. radiate out through cytopasm. form spindle fiber during cell division. cilia and flagella.
  2. structure: straight, hollow, diameter 25nm, heterodimer (alpha tubulin, beta tubulin-bound by noncovalent bond) subunit carry GTP/GDP. protofilament (13 parallel chain for alternating alpha and beta). have structural polarity, beta found at + end, alpha found at - end.
  3. Regulation/growth: grow from microtubule-organizing center (aka centrosome) through nucleation, a process in which filament is elongated outward by adding subunit to + end. growth has dynamic instability.
  4. Side-binding Proteins: MAPs (stability), capping protein (stabilize), cross-linking proteins (structure), severing protein (katnin/ control length of mt)
  5. microtubule toxin: colchicine (cause depolymerization), Taxol (cause increase tubulin polymerization)
  6. clinical significants: stabilize, destabilize microtubual agendt can activate or deactivate cancer cell because it affect mitotic spindle fiber in dividing cells.>> antimitotic drug.
Term
Microtubular growth, centrosome, dynamic instablity and gamma tubulin ring, stathmin
Definition
  1. gamma tubulin ring complexes contained in centriole. serve as template that nucleate the first microtubule rings composed of 13 alpha beta tubulin heterodimers.
  2. - end associate with centrosomes, + end grows rapidly outward >> astral microtubules.
  3. dynamic instability>> alternated phase of slow polymerization and rapid depolymerization. controlled by GTP hydrolysis. monomer with GTP bind more strongly then monomer with GDP. this give flexibility by permitting shape change, location change.
  4. stathmin (minomer-sequestering pt)  bind to monomer, render it unavailable for polymerization.
Term
Microtubule associated protein (MAPs) vs. catastrophins
Definition
  1. MAPs bind to sides of microtubules and increase stability. regulate growth and positioning of microtubule, convert cell to a strongly polarized structure>>> longer, less dynamic microtubule.
  2. catastrophins: family of kinesin, bind to microtubule "+" ends and induce disassembly or catastrophe.
Term
Capping protein (MAPs) vs. gamma tubulin ring complexes
Definition

- capping protein: bind and stabilized the free "+" end of mt.

-gamma tubulin ring complexes: capped "-" end of the mt.

Term
Location of actin filaments (microfilaments)
Definition

- cell cytoplasm

- in most cell, form bundles, meshes below cell membrane to serve as component of cell cortex (or cortical cytoskeleton), which provides structure support for cell.

- form structure such as microvilli, or stress fibers (contractile bundles) in cytoplasm that act like cell's muscle.

-provide structures for lamellipodia and filopodia important in cell crawling, or the contractile ring tha tpinches cytoplasm during cell division.

Term
structure of actin filaments
Definition
  1. actin monomer= G-actin
  2. G-actin carries ATP/ADP. monomer binds to form protofilaments.
  3. actin monomers align so that their ATP binding sites point in the same direction, which actin filaments structural polarity.
  4. atp-binding cleft on actin point to "-" end (pointed end), another end is "+" end (barbed end)
  5. two actin profilaments twist around to form long filamentous polymer, F-actin.
Term
maintenance of actin filaments
Definition
  1. add to "plus end" (polymerization) while monomer remove from "minus end" (depolymerization)>>>Treadmilling. Hydrolysis of ATP provide this.
  2. like dynamic instability in Mt, treamilling provide flexibility and permit cytoskeletal to change shape and location
Term
Regulation of actin filament growth
Definition
  1. Nucleation of actin filaments by formin and actin-related protein (APR 2/3) complex
Term
accessory proteins associated with actin filaments
Definition
  1. Growth depend on concentration of free G-actin monomers. whcih is controlled bu monomer-sequestering protein thymosin (prevent polymerization), and profilin (aids addition of monomers)
  2. also monitored by other Side-Binding protein: tropomyosin (increase stability, prevents interaction with myosin), Cofilin (actin depolimerizaing factor, cause protofilaments to twist tighly around each other, cause increase rate of actin filament treadmilling)
  3. capping protein: CapZ , Gelsolin bind to + end and inactivate, prevent further growth. - end may be capped by ARP2/3 or tropomodulin (in muscle cells).
  4. severing protein:gelsolin superfamily, these required high level of cytosolic Calcium ion. Gelsolin activity increase with increase cytoplasmic calcium concentration.
  5. Cross-linking protein:
  • actin bundling proteins (ex. fimbrin, villin, and alpha-actinin)hold actin filaments together in rope-like bundle in microvilli, or filopodia.
  • Gel-forming protein (ex. spectrin, filamin) organizes actin filaments into loose gel-like meshwork within cell cortex or lamellipodia.

 

Term
Point of actin filament attachments
Definition

form bundles and meshes below cell membrane where they serve as component of cell cortex.

 

ex. RBC actins associate with spectrin heterotetramers. Spectrin-actin mesh is liked to cell membrane by ankyrin and band 4.1 protein. ankyrin also anchor spectrin-actin mesh work to integral membrane like band 3 protein.

Term
adherent junction (cell to cell junctions)
Definition
  1. adhesion belt or zonula adherens, bundles of cortical actin filaments attached to transmembrane adhesion protein called cadherins, through anchor proteins ( alpha, beta, gamma-catenins, viculin, alpha actinin, and formin-1)
Term
focal adhesions (cell to matrix junction)
Definition

bundles of cortical actin filaments are attached to transmembrane adhesion protein called integrins, through a set of intracellular anchor protein (talin, alpha actinin, filamin, viculin)

Term
microfilament toxins and clinical significants
Definition
  1. affect by some toxin produce by fungal and sea sponge. ex. latrunculin binds to minues end causing depolymerization. Phalloidin binds and stabilizes actin filaments, causing increased polymerization. cytochalasin bind to plus end, prevemt additon of G-actin.
  2. Wiskott-Aldrich syndrowm (WASP) family: defects in protein that activates ARP2/3 complex
  3. Elliptocytosis: autosomal dominant, oval RBC caused by defective self-association of spectrin subunits, abnormal binding of spectrin to ankyrin, binad 4.1, and abnormal glycophorin.
  4. Sperocytosis: autosomal dominant, involve deficiency of spectrin

elliptocytosis and sperocytosis caused anemia, jaundice and splenomegaly.

 

Term
Location of intermediate Filaments
Definition

extend across cytoplasm bind to anchoring junctions (desmosome, hemidesmosome)

 

fx: strengthen cells subjective to mechanical stress.

abundant in muscles and nerve axon cells.

 

Term
Structure and Formation of intermediate filaments
Definition
  1. rope-like. monomer=elongated fibrous molecule with  central alpha-helical domain, and two non-helical region at both end.
  2. two monomer form intercoiled (coiled coil) dimer. a pair of dimers assemble to form tetrameric subunit.
  3. tetrameric subunit is basic subunit for intermediate filament (like G-actin)
  4. lack a structural polarity since amino terminal and carboxyl terminal are align side-to-side.
  5. eight parallel protofilament form intermediate filament.
Term
Points of attachment of Intermediate filaments
Definition
  1. desmosomes (cell-to-cell junctions): intermediate filament (keratin or desmin) attacged to transmembrane adhesion protein called desmoglein and desmocollin, through plakoglobin and desmoplakin.
  2. hemidesmosomes (cell to matrix junction): intermediate filaments attached to transmembrane adhesion protein called integrin alpha6 beta4 through protein plectin.
Term
cross-linking proteins of intermediate filaments
Definition

package into bundles by cross-linking protein.

  1. filaggrin: bundles keratin
  2. plectin: bundles vimentin.
Term
clinical significance of intermediates filaments
Definition

expression of mutant keratin caused inherited diseaseS:

  1. epidermolysis bullosa simplex (EBS): skin blister after minor trauma. mutated keratin 5 or 14.
  2. eidermolytic hyperkeratosis (EH): excessive keratinization of epidermis. mutated Keratin 1 and 10
  3. epidermolytic plantopalmar keratoderma (EPPK): skin disease producing fragmentation of epidermis of palms and soles, caused mutation of keratin 9 gene.
  4. amyotrophic leateral scelrosis: caused by accumulation of neurofilament in motor neuron>> fatal muscle atropy.
  5. laminopathies: defects in pt of nuclear envelop like lamins. mutation of lamin A of C gene cause muscular dystrophy and neuropathy.

 

Term

Motor protein

 

definition and fx

Definition

are proteins tat move along polarized cytoskeletal filaments.

 

fx: carry cargo (vesicles, organelles) from one place to a different location.

 

 

Term

Motor Protein

 

general structure

Definition
  1. contain head region (motor domain) that ove along actin fil or microtubule. energy from ATPase activity.
  2. contain a tial that binds specific cargo.
Term
Myosins-motor proteins that move along actin filaments
Definition
  1. types: myosin I and II. all but myosin VI move toward the "+" end of F-actin filament.
  2. Myosin I (unconventional myosin) found in all cell, has motor head and a tail. head has a light chain. head uses ATPas activity to provide energy for cycle of binding, detachment, and rebinding.
  3. Myosin II (conventional myosin) found in muscle and some non muscle cells. composed of a pair of heavy chains held by tail, and four light chains bind to head domain. Has two motor heads. associate with contractile activity, required for cytokinesis and translocation.
  4. Myosin V (unconventional myosin): double headed with coiled double tail, can be found in all cells. Heads bind actin filamin. Tails bind to Rab27a, a receptor on vesicle membrane. Myosin Va mediates vesicular transport along actin filament.
Term
Motor proteins that move along microtubules
Definition

1. Kinesis: heavy chain homodimers, have two globular ATP-binding motor heads associated with four light chains and a cargo-carrying tails. Move toward "+" end of microtubules (away from centrosomes). Fx to move vesicles, mitochondira and positioning of ER.

2. Dyneins (cytoplasmic): heavy chain homodimers, have two globular ATP-binding motors head associate with a number of light chains, and a cargo-carrying tails. Move toward the "-" end of microtubules (toward the centrosome). Fx to move vesicles and positioning golgi apparatus.

3. Dyneins (axonemal): heterotrimers, with three motor heads. specilized for rapid sliding movements of microtubles that drive beating of cilia and flagella.

 

clinical significant: discruption of actin transport of melanosomes caused by mutation in Rab27a or myosin Va>> griscelli syndrome.

Term

cilia and Flagella

 

hair like celllar appendages built from core of stable microtubules arranged in a bundle, an axoneme, and a form of motor protein called axonemal dynein. >> cell motility.

Definition
  • ciliated cells: epithelium of respiratory and oviduct tract.
  • flagellated cells: sperms.
  • axonemal transport: flagella (intraflagellar transport) and cilia (intraciliary transport) deliver tubulin dimers to distal growing end of cilial and flagellar microtubules.
Term

arrangement in cilia and flagella

 

9+ 2 arrangement

Definition

9 doublet microtubles, surround 2 central singlet microtubles.

 

microtubules cross-linked by nexin

 

nexin caused microtubules to be fixed in place, so when axonemal dynein attemp to move twoard "-" end upon ATPase, it will cause cilia or flagella to bend.

 

cilia and flagella attached to cytoplasm through basal bodies. each basal body is composed of 9 microtubule triplets arranged in "cartwheel"

Term
Organizing center for cilium and flagellum
Definition
basal body
Term
clinical significance involving cilia and flagella
Definition

Bardet-Biedl syndrom (BBS): defect assembly of basal body and cilia>> retina dystropy, obesity

 

Kartagener's syndrome: structural abnormality in the axoneme.  immortile sperm, brachiectasis.

Term
cell crawling
Definition

3 steps dependent n actin filament rich cell cortex beneath plasma membrane.

 

  1. protrusion: assemble in direction that want to move, and push plasma memb outward. flipodia (1D actin bundle), lamellipodia (2D sheet-like actin layer), pseudopodia (3D gel like actin mesh). 
  2. attachment: integrin adhere to extracellular matrix and actin filament. focal adhesion contact.
  3. traction: cell push the trailing cytoplasm forward using anchorage sites. utilize interation with motor Myosin II.

treamilling occur during crawling.

 

Term
intraneuronal transport
Definition
  1. actin filament: cortex of axon, myosin V helps moves intracellular material.
  2. neurofilament (intermediate): structural support.
  3. microtubules: In axon, minus end point toward cell body, plus end points toward axon terminal. in dendrite, not polar, plus end points toward dendrite tip, others point back toward cell body.
  4. kinesis (plus-end directed motor protein): fast anterograde axonal transport. move stuff from body to terminal.
  5. dyneins (minus end directed motor protein): fast retrograde axonal transport. moving cargoes in the opposite direction. 
  6. slow anterograde transport: moves cargoes to terminals.
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