Histology / Cell Biology Flashcards
How do microtubules grow and shrink?
What components or subunit form the microtubules?
Microtubules grow out towards the periphery of the cell from the MTOC (microtubule organizing center). They possess a growing end (plus end) and an non-growing end (minus end) that is anchored in the MTOC.
They grow outwards due to tubulin dimers (alpha and beta) that polymerize and attach to the plus-end (growing end). They shrink when tubulin dimers depolymerize from the plus end.
Polymerizaiton requires GTP and Mg2+
What are the clinical implications of microtubule polymerization/depolymerization mechanisms? (hint:cancer)
Many anti-tumor drugs inhibit or freeze this polymerization/depolymerization which stops a cell from forming a spindle and replicating. (ie - Taxol)
What are the 5 functions of microtubules in cells?
- Vesicles - Intracellular vesicular transport
- Motility - Movement of cilia and flagella
- Replication - Attachment of chromosomes to mitotic spindle and movement during mitosis & meiosis
- Migration - Cell elongation and movement during migration
- Cell Shape - Maintenance of cell shape, particular its asymmetry
What are molecular motor proteins? Name 2 types.
How do they work?
Molecular motor proteins help move material (vesicles) along microtubules throughout the cell. They also help move chromosomes during mitosis and cytokinesis. ATP is required.
There are 2 types:
- Dyneins - move from plus end–>minus end. They move chromosomes along spindle fibers during mitosis
- Kinesins - move from minus end–>plus end. They help push chromsomes apart during mitosis (Push overlapping microtubles in opposite directions).
What disease is associted with absence of dynein arms?
**Kartengers syndrome **
Dyenin motor proteins are required in motile cilia. Without them sperm can not function (infertility) and respiratory mucous can not be cleared (respiratory issues).
Colchicine is a drug that binds to tubulin molecules and prevents polymerization. How would this drug impact neurtrophils which need to migrate to sites of infection?
Preventing polymerization of microtubules would inhibit migration of neutrophils.
This is a treatment for gout which is caused by acute inflammation.
What are the functions of actin filaments?
- Anchorage and movement of membrane protein – cell junctions and focal adhesions
- Formation of the structural core of microvilli
- Locomotion of Cells – growing actin extend processes (lamellipodia) and cell can crawl or migrate
- **Extension of Cell processes **
How do actin filaments grow and shrink?
Actin filaments grow at both ends through the polymerizatin of actin molecules. There is a fast growing end known as the plus or barbed end. And there is a slow growing end known as the minus or pointed end.
ATP is required to polymerize the actin.
What is the difference between F-Actin and G-Actin?
F-Actin = Free actin molecules in the cytoplasm
G-Actin = Polymerized actin molecules
In general, what do actin binding proteins (ABP) do?
Responsible for filament organization. They also enchance or prevent polymerization.
What is the function of the acting binding protein: GELOSIN.
Cuts actin filaments into shorter lengths.
What is the function of the acting binding protein: TROPOMODULIN.
Blocks further addition of actin molecules by binding to free ends.
What is the function of the acting binding protein: Spectin, Protein 4.1, and Protein 4.9.
Cross-link actin filaments to each other and form filament bundles
How does actin promote cell movement?
Growing actin can extend processes, called lamellipodia, which allows the cell to crawl and migrate.
What is the function of the acting binding protein: FASCIN & FIMBRIN.
Cross-link actin filaments into parallel arrays, creating bundles.
What is the function of the acting binding protein: MYOSIN I & MYOSIN II.
Myosin I and Myosin II are motor proteins that contract actin filaments. Myosin II is found in muscle cells. Myosin I is found in non-muscle cells.
Cytochalasin B and cytochalasin D, effects
actin polymerization. A mushroom toxin, Phalloidin, also effects actin polymerization. How does each drug/toxin work specifically on actin filaments
Cytochalasin B and cytochalasin D bind to the ends of actin filaments, preventing polymerization.
Phalloidin also binds to actin filaments, but stabilizes them, preventing depolymerization.
Describe the structure of intermediate filaments.
In general, what is the role of intermediate filaments?
Are they constantly changing shape, like actin filaments or microtubules?
Intermediate filaments play a structural role in cells. They do NOT change shape constantly (no dynamic instability).
Their structure is as follows:
- Subunits: rod-shaped proteins with globular domains at either end. There are many types of subunits - tissue specific.
- Two subunits are twisted around each other to form a coiled dimer. Two dimers twist around each other to make a staggered tetramer.
- Tetramers are stacked and bundled to form bigger filaments.
- They are non-polar
What are class I and II intermediate filaments called?
In what cells types are they predominately found?
Keratins
Keratins are found in different epithelial cells. Account for most of the intermediate filaments in the body.
What are class 3 intermediate filaments called?
In what cells types are they predominately found?
Vimentin and Vimentin-like
Class 3 IF contains 4 proteins:
- Vimentin - fibroblasts (mesoderm cells)
- Desmin - Muscle Cells
- Glial Fibrillary Acidic Protein (GFAP) - Glial Cells
- Peripherin - Nerve Cells
What are class 4 intermediate filaments called?
In what cells types are they predominately found?
Neurofilaments
Neurofilaments are found in nerve cells and muscles cells
What are class 5 intermediate filaments called?
In what cells types are they predominately found?
Lamins
Located in the nucleus of All nucleated cells
What are class 6 intermediate filaments called?
In what cells types are they predominately found?
Beaded Filaments
Located in eye lens fiber cells
There are a number of disease associated with Intermediate filaments - Alzheimers disease, Alexander disease, and alcoholic liver cirrhosis.
In general, what types of defects are occuring?
Describe how IF play a role in each disease.
In general, many disease are caused by the improper assembly of intermediate filaments. These altered IF, lead to accumulation of IF in the cytoplasm or extracellular fluid.
- Alzheimers Disease – changes in neurofilaments produce neurofibrillary tangles
- Alexander Disease – mutations to GFAP gene produce accumulatoins of intermediate fibers (Roesenthal fibers in astrocytes-brain)
- Alcoholic Liver Cirrhosis – predominant feature is inclusions composed of keratin intermediate filaments. These inclusions are called Mallory bodies.
