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Basic Principles Of Medicine 1-FTM 1 > Cells 2 > Flashcards

Cells 2 Flashcards

1
Q

What are the components of cytoskeleton ?

A
  1. Actin filaments (microfilaments)
    - actin
    - 7nm diameter
  2. Intermediate filaments
    - 6 classes, numerous proteins
    - 8-12 nm diameter
  3. Microtubule
    - tubulin
    - 25 nm diameter
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2
Q

What are the functions of the cytoskeleton?

A
  • structural support & stability
  • organization
  • cell division
  • cell movement
  • tracks for motor proteins to move organelles & vesicles within cells
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3
Q

Describe the structure of microtubules

A
  • Non-branching, rigid, hollow tubes
    • a and B tubulin protein subunits

Polar

  • minus (-) end
  • plus (+) end
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4
Q

What are the functions of microtubules ?

A

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

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5
Q

Describe the structure of centrioles

A

9 Triplets of microtubules arranged around a central axis

-Each triplet consists of 1 complete and 2 incomplete microtubules fused

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6
Q

What are the functions of centrioles?

A

-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
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7
Q

Explain the structure of the centrosome

A

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
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8
Q

What is the function of the centrosome?

A

-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
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9
Q

What are the mitotic spindle poisons?

A

Colchicine

Taxol(palcitaxel)

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10
Q

What is colchicine?

A

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
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11
Q

What is taxol (palcitaxel)?

A

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
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12
Q

Describe microtubules

A

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
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13
Q

Describe microtubule associated proteins (MAPs)

A

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
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14
Q

Describe the Dynein family as microtubule motors

A
  • 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

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15
Q

Describe the kinesin family as a microtubule motors

A
  • Move in the (+) direction along microtubules
    • anterograde
  • binding sites for vesicles, organelles, microtubules
  • about 40 distinct kinesins humans
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16
Q

Explain the structure and function of the cilia & flagella

A

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
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17
Q

The cilia is anchored to the …

A

Basal body

-thin, dark staining band at base of cilia

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18
Q

What is the function of the cilia?

A

Move fluid and particles along epithelial surfaces

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19
Q

Describe the structure of the cilia

A

Microtubule-based, hair like structure

- motile
   - beat in synchronous pattern

9+2 microtubule arrangement

Pair of dynein arms

- motor protein
- binds adjacent microtubule
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20
Q

Explain the primary cilia as a sensory antennae

A

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
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21
Q

Briefly describe the structure of the primary cilia

A
  • 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
22
Q

Describe the structure of the intermediate filaments

A

Rope-like filaments

Structure: formed by non-polar & highly variable subunits

23
Q

What are the functions of the intermediate filaments ?

A

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

24
Q

What are the classes of intermediate filaments?

A
  • keratins
  • vimentin & vimentin-like
  • neurofilaments
  • lamins
  • beaded filaments
25
Q

Explain keratins as intermediate filaments

A

Acid & basic cytokeratins

  • diverse group
    • over 50 isoforms

-found in all epithelial cells

26
Q

explain vimentin & vimentin like as intermediate filaments

A

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
27
Q

Explain neurofilaments as intermediate filaments

A

-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

28
Q

Explain the lamins as intermediate filaments

A

Found in nucleus of all nucleated cells
-nuclear lamina

Lamin A & B proteins

29
Q

Explain beaded filaments as intermediate filaments

A

-Eye lens-specific group

30
Q

Contrast the types of actin

A

G-actin= free actin molecules in cytoplasm

F-actin= polymerized actin in a filament, ATP dependent

31
Q

Describe the structure if actin filaments

A

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

32
Q

What is the function of the actin filament?

A

Variety of cell functions

  • anchorage
  • structural core of microvilli & stereocilia
  • cell motility
    • locomotion
  • extension of cell processes
33
Q

What are the actin & fungal toxins?

A

Phalloidin & cytochalasins

34
Q

What is phalloidin?

A
  • 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
Other toxins (amatoxins) are responsible for the toxic effects following oral ingestion 
     -liver and kidney failure & death 4-8 days after consumption
35
Q

What are cytochalasins?

A
  • other fungal products
  • block polymerization of actin
  • Can be used to inhibit cell movement, division, & induce programmed cell death
36
Q

Describe microvilli

A
  • 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
37
Q

Describe the structure of stereocilia

A

Unusually long microvilli
-up to 120 um in length

Actin filament bundle anchored to terminal web

38
Q

Where can stereocilia be found?

A

Limited distribution

  • Epidydmis
  • proximal Ductus deferens
  • sensory hair cells of inner ear
39
Q

Describe myosin as an actin motor

A

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

40
Q

What are the myosin structural changes for actin motors?

A

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

41
Q

How is actin involved in cell movement?

A
  • 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

42
Q

How does actin help with plasma membrane protrusions?

A

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

43
Q

Explain the cell movement- lamellipodia

A

Common example- fibroblasts of connective tissue

Complex & integrated process

  1. Protrusion
    - Actin polymerization at plus (+) end protrudes lamellipodium
  2. Attachment
    • Focal adhesions anchor the actin cytoskeleton to the extracellular matrix via integrins proteins
  3. Contraction
    - Bulk of the training cell & cytoplasm is drawn forward
44
Q

What is chemotaxis?

A

Movement within tissue along a chemotactic gradient towards the source of inflammation

  • N-formylated peptides
  • Peptides attached to extracellular matrix
45
Q

Summarize neutrophil migration

A

Extravasion

  1. Rolling
  2. Activation
  3. Adhesion
  4. Transendothelial migration
    Process of diapedisis
    -Extension of a pseudopod between endothelial cells
    -Pass the basement membrane into the tissue.
46
Q

What are inclusions?

A

Cytoplasmic or nuclear structures formed from metabolic products of the cell

Pigments- membrane bound

47
Q

Describe Lipofuscin as an inclusion

A

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

48
Q

Describe hemosiderin as an inclusion

A
  • 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

49
Q

Describe melanin as an inclusion

A
  • 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
50
Q

Describe glycogen as an inclusion

A
  • Non-membrane bound, TEM dense bodies
    • single(beta) 20-30nm particles or rosettes (alpha)
  • Storage form of glucose
    • Catabolism releases glucose for energy
51
Q

Describe lipids as an inclusion

A

-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

Basic Principles Of Medicine 1-FTM 1 (39 decks)

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