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Cytoskeleton is composed of three filament networks
1) ACTIN MICROFILAMENTS
2) INTERMEDIATE FILAMENTS – less dynamic than actin and microtubules
3) MICROTUBULES
*only eukaryotes, 3d structure that fills cytoplasm
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Cytoskeleton filaments are polymers of subunits that CYCLE BETWEEn AN ASSEMBLED AND UNASSEMBLED STATE very quickly
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Intermediate filaments characteristics
Toughest can withstand the most stress w/o breaking because they are constructed from subunits like a rope
**IF network can survive death of cells *hair, fur, nails, outer covering of skin
Mechanical stability to the whole cell for cytoplasmic intermediate filaments and nuclear envelope to nuclear IF
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Intermediate filaments 4 general categories that each express a characteristic type of cytoplasmic IF and example
Keratine – epithelia
Vimentin and vimentin related – connective tissue, muscle cells, and glial cells
Neurofilaments – nerve cells
Nuclear lamins – all animal cells (all cell types contain nuclear lamin)
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metastasis(definition)
The spread of a disease process from one part of the body to another, as in the appearance of neoplasms in parts of the body remote from the site of the original tumor; results from the dissemination of tumor cells by the lymphatics or blood vessels or by direct extension through serous (body) cavities)
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Type of cytoplasmic IF produced by cells in a tumor tells the tissue type of origin of the tumor
- This is used extensively by pathologists for characterizing the tissue of origin of a tumor celL that may have metastasized
- Unlike the actin and tubulin isoforms, IF protein classes are widely divergent in sequence
- Can biopsy a tumor from any location and test for the type of IF it contains-in this way, can determine in what tissue type the tumor originated Cell/tissue type of origin influences treatment of tumor
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Nuclear lamins function
Line inside of the nuclear enevelope and give mechanical strength to nuclear membrane
**only cytoskeleton filaments that are not cytoplasmic
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Actin characteristics 4
Found in all human cells
50% of actin aubunits are assembled into filaments, other is free
Subunits rapidly cycle back and forth between being free and then assembled
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Actin filament assembly
Its composed of a 2 stranded helix with plus end and minus end, the subunits add on the plus end and fall of at the minus end. G actin unassembled globular actin monomers while F actin assemble actin filaments
**because actin is abundant, when polymerizes it can push out plasma membrane to change shape of the whole cell within seconds, the way it is polymerized inside the cell is the determination of cell shape, can occur at the same time in the same cell
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Actin function 3
Cell motility
Contraction
Determine shape of cells surface
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Function of microvilli contain actin and are membrane protrusions that increase the surface area of cells 4
Absorption
Secretion
Cellular adhesion
Mechanitransduction
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Reason for surface area needing
Needed for lots of transporters (intrinsic membrane proteins with transmembrane domains) to take up ingested materials
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Actin binding proteins types 3
Cross links
Severs
Nucleates actin to form a different structure
**actin can form so many structure due to large number of ABP
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Actin binding proteins are located at PM so most assembled in the cell is located right under plasma membrane
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Myosin define
An active Motor protein that depend on the interaction of myosin with actin that can slide one actin filament past another or moves cargo such as vesicles along actin filaments using ATP as fuel
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Actin-myosin form muscles of the cell and become more specialized and assemble in thin and thick filament (power muscle contraction) ex contractile ring of cell division is formed from actin and myosin filaments
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Actin rearrangements power whole cell locomotion so the cells in the body can crawl across surface. The crawling cell pushes the cell forward to form lamellipodium
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Lamellipodium define
Forming from actin polymerization crawling pushes the cell forward to create this formation
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Stress fibers are contractile actin-myosin bundles found in non-muscle cells
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Mcirotubules location, subunit dimer, function of dimers
All human cells
Are heterodimers of A and B tubulin
Tubulin heterodimers rapidly cycle back and forth between being free and assembled which when assembled form a hollow microtubule
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Microtubules function and formation 3
Determine position of intracellular organelles and provide tracks for intracellular transport for components such as vesicles and organelles with motors
Form cilia and flagella and mitotic spindle
Assisted in functions by microtubule associated proteins
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2 types of MT based motors that use ATP to power movement
Kinesin-transport materials toward + end
Dynein – transports material toward – end
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Function of cilia and flagella
Motile by projections from cell surface that are made up of MT and covered by extension of PM and designed to move cell itself or to move substances like mucus or extracellular fluid overlying the ciliated cells
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Flagella and cilia similarities and difference
Nucleated by basal body (like a centrosome)
Microtubules in cilium or flagellum are arranged in a 9+2 array (used to recognize MTs on Ems)
Flagella longer than cilia
Both grow out of MTs in a centriole basal body with same 9 triplet of MT structure
Cell have multiple cilia but one flagellum
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Flagellum and ciliated cells human body location
Only cell in human body that has one is spem
Found in respiratory tract (drive debris out of lung) fallopian tubes (drive egg from ovary)
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How microtubules organize themselves?
Assembly gives a + and a – end. They grow and shrink by add and loss of tubulin heterodimers at + end inside the cell. Tubulin heterodimers add on GTP form and fall of GDP form
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Microtubules organizing center (MTOC) location
Inside of the cell, grow out of a structure centrosomes composed of 2 centrioles surrounded by cloud of proteins called pericentriolar material (cell division)
Located on one side of nucleus under golgi stacks
**motc caps minus end of MT and + end grows out to periphery
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Gamma-tubulin ring complex function 3
Is a component of the pericentriolar material of MT
It nucleates or provides start for MT to grow hundreds from 1 centrosome
MT grows and shrinks independently of its neighbors
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Axonemal dynein defined & function
Motor for beating of cilia and flagella that slides one MT doublet past another bends cilium or flagellum by using ATP
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Ciliopathy define
Genetic disorder of cellular cilia. Have overlapping clinical features in multiple organs because cilia function in many diff tissues
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Primary cilia dyskineasia (kartenger syndrome) defined
Rare autosome recessive genetic disorder that causes lack of axonemal dynein in motile cilia (action of cilia lining) i.e fallopian tube, respiratory tract
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2 main consequences of impaired ciliary function
Reduced of absent mucus clearance from lungs leading to susceptibility to chronic respiratory infections
Infertility resulting from immotile sperm
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How microtubules form the mitotic spindle and their part in mitosis?
MT disassemble from interphase conformation and reassemble to form mitotic spindle, centrosome double in dividing cells prior to mitosis, plus ends of MT plug into kinetochores on chromosome and the MT pull sister chromatids apart into 2 daughter cell
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2 clinical uses of anti-MT drugs and why used
Anti cancer drugs – MT specific drugs are important because if you inhibit MTs ability to form the mitotic spindle you inhibit cell division
Treatment for gout
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MT specific drugs 4 and actions
Taxol – binds and stabilizes microtubules
Colchicine, colcemid – binds and subunits and prevents their polymerization
Vinblastine, vincristine – binds subunits and prevents their polymerization
Nocodazole - binds subunits and prevents their polymerization
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How multiple cytoskeletal filament network work together for certain functions?
Actin and MT-actin forms lamellipodium to cell crawl. Actin pulls cells forward while MT guide direction of growth. Inhibit MT function, you can inhibit cell crawling
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Gout caused and symptoms
Formation of uric acid crystals in joints
Painful swelling and attracts leukocytes that amplify the inflammation
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How can colchine treat gout?
Prescribed for acute attacks at low levels for prevention of gout
By inhibiting functions MT, colchicine prevents the migration of leukocytes to the region and thereby reduces the associated inflammation of gout
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How do well attach themselves to other cells?
Cadherins (1st type of cell adhesion molecule) transmembrane proteins
Adhere one cell to another in a calcium dependent fashion
**calcium concentration doesn’t regulate binding cause calcium in always high in extracellular fluid
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Interactions between cadherins ectodomains from apposed cell mediate cell to cell contact where intacellular region functionally links cadherins to underlying cytoskeleton
**2 cells of the same type are attached
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Desmosomes (maculae adherens) define
Junction between 2 cells that contain cadherins and link to tough IF (i.e. tissue layers)
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Pemphigus define and cause
Rare autoimmune disease that form group of blistering (“” vulgaris is common type)
Autoantibodies form against a component of desmosome which normally holds skin together.
Auto antibodies attack and destroy desmosomes skin separates from each other and becomes unglued causing blisters that slough off and turn into sores
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Integrins (2nd type of cell adhesion molecule)
Adhere one cell to its non cellular surroundings i.e link cell to component of the cell matrix
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Integrins defined and function
Transmembrane heterodimeric proteins that constitute the main receptors for extracellular matrix components
Sense whether adhesion can occur
Link to cytoskeleton on inside of cell (actins of IF)
**many types exist, one cell can have multiple types of surface
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How integrins interactions with ECM coordinate with the changing cytoskeleton, metabolism, and gene expression inside of cell?
Before ligand binding, intergrins activate signal transduction pathway that mediate cellular signals such as reg of cell cycle, organization of intracellular cytoskeleton, and movement of new receptors to the cell membrane
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How integrins interact with ECM and (cytoskeleton) ligand attached?
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Activated by binding of ECM and cytoskeleton causes conformational change in integrins (inactive if no binding)
When
activated, integrins trigger signal transduction, informing the cell of
chemical composition and mechanical status of ECM. This allows for
rapid and flexible responses to events on cell surface (can activate in
lipid rafts)
Activated by binding of ECM and cytoskeleton causes conformational change in integrins (inactive if no binding)
When activated, integrins trigger signal transduction, informing the cell of chemical composition and mechanical status of ECM. This allows for rapid and flexible responses to events on cell surface (can activate in lipid rafts)
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