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How often do the following cells divide? Where are they located?
1. Labile
2. Stable
3. Permanant
1. constantly divide (includes oral mucosa cells, hematopoietic)
2. re-entry (like entering G0, then go back): liver
3. incapable of dividing (neurons, cardiac myocytes)
What is cyclosporine?
An immunosuppressant used to prevent organ rejection in transplant patients
Length of:
1. G1
2. S
3. G2
4. M
1. 5 hours
2. 7 hours
3. 3 hours
4. 1 hour
a. Prophase - 36 min
b. Metaphase - 3 min
c. Anaphase - 3 min
d. Telophase - 18 min
What happens in G1?
increase in cell size
RNA & protein synthesis
asks: is the environment stable?
What happens in S phase?
DNA duplication
centriole duplication
What happens in G2?
synthesis of proteins
synthesis of maturation promoting factor (MPF) (ex: cyclin-CDK complex)
increase in cell size
asks: is all DNA replicated? is all DNA damage repaired?
What happens in G0?
quiescent cells exit G1 and enter resting stage where cell performs its function without actively dividing
What is centrosome?
microtubule organizing center
What is a centriole?
Used by Animal Cells to produce spindle fibers that help with cell division
What happens in prophase?
Chromosomes condense
Nuclear membrane intact
Centrioles separate
Spindle apparatus formed by microtubules
What happens in prometaphase?
sister chromatids become attached to the kinetochore
nuclear envelope breaks
What happens in metaphase?
Chromosomes line up in the middle of the cell
Sister chromatids are attached to spindles on opposite poles
What happens in anaphase?
- Sister chromatids split and move to either pole (Disjunction)
- Anaphase-promoting complex (APC) trigger chromatid separation, degrading cyclin B
What is anaphase-promoting complex?
ubiquitin ligase that initiates sister chromatid separation
What happens in telophase?
Nuclear membrane reforms
Chromosomes decondense
Formation of contractile ring
What happens in cytokinesis?
division of the cytoplasm by contractile ring
The miotic spindle is made of
microtubules
The contractile ring is made of?
actin and myosin
Cyclins activate ______________, which also have inhibitors, all of which exert negative control over the cell cycle
Cyclin dependent protein kinases
Amount of CDK is _______.
Amount of Cyclin-CDK ______.
constant
varies
Cyclins are _____ by ubiquitin proteins (like APC)
degraded
CDK2
What are the functions of the cytosol?
- signal transduction (secondary messengers, protein-protein interactions)
- mRNA translation
- biochemical rxns (pentose phos. path, glycolysis, gluconeo.)
- contains cytoskeleton (microfilaments, microtubules, and intermediate filaments)
- proteasomal degradation
What are the functions of the cytoskeleton?
- maintains/ changes cell shape
- whole cell movement
- contraction
- structural integrity
Difference between G-actin and F-actin?
G-actin: monomer globular protein
F-actin: polymer filamentous chain
Myosin head with ____ attaches to ____ binding sites, undergoing configuration changes, moving _____ filament
ADP
actin
actin
Calcium is released from the ____ and binds to the troponin-tropomyosin complex to facilitate ______
sarcoplasmic reticulum
muscle contraction
In cardiac muscle contraction, the process uses _______, ______, and _______.
Cells are separated by _____ ______
adherens, desmosomes, and gap junctions
intercalculated disks
Smooth muscle contraction occurs when calcium enters the muscle, activating the _____ _______ _____ ______, which phosphorylates the regulatory ____ _____, enhancing myosin ATPase activity.
myosin light chain kinase
light chain
In non-muscle cells, actin functions include:
- maintaining cell shape
- motility
-cargo transport
The terminal web controls ______ and ______. It contains actin, _____, and ______
shape and movement
myosin and spectrin
Give examples of cells that express the following:
1. spectrin I
2. spectrin II
3. alpha-actin
4. pystrophin
1. RBCs (erythrocytes)
2. all other cells
3. muscles
4. skeletal muscle
Microvilli contain a _____ core, and its functions include:
microfilament
increased plasma membrane surface to enhance absorption and secretion of molecules
Myosin I, IV and V move cargo towards ___ end of vesicle
myosin VI moves cargo towards the ____ end
plus
minus
Microtubules are made of ______. They require ____ to polymerize.
tubulin (alpha heterodimer)
GTP
Microtubule functions
- transport/ secretion of vesicle cargo
- separation of chromosomes in mitosis/ meiosis
- contribute to cilia, flagella, motion etc
What is dynamic instability? How is it regulated?
the constant growth and degradation of microtubules. This is when GTP hydrolysis occurs fast, making the microtubule shrink faster than it grows
Its regulated by microtubule associated proteins (MAPs) by capping the plus end, preventing disassembly
What are the types of microtubules associated proteins (MAPs)?
Assembly = MrMAP and tau protein
Disassembly = Stathim and Katamin
Cargo transport is mediated by ______. The direction of traffic depends on _________. Which protein move in which direction?
motor proteins
protein domain (N-terminal=(+), C-terminal=(-))
Kinesin moves towards (+) end
Dynein moves towards (-) end
What does dynein do in normal and abnormal flagellum?
dynein= microtubule bending
abnormal=microtubule sliding
What is cilia's function?
used the increase cell surface area and increase absorption
contains hexagonal 9+2 array
What is the function of intermediate filaments?
support cell shape and fix organelles in place
What are an intermediate filaments composed of?
They are composed of hetero fiber proteins formed spontaneously and have no polarity
Examples of intermediate filaments
Cytoplasmic intermediate filaments include keratin, Neuro filaments, and Vimentin. It also includes nuclear lamina.
What are examples of homophilic adhesion?
Cadherin and IG like. Cell adheres molecules binding to another solid adhesion molecule (CAM)
What are examples of heterophile adhesion?
Selectin (CAM binding to protein)
What are Integrins and their function?
They are heterodimer's made of alpha and beta chains. Receptors are tissue and ligand specific. They interact with the cytoskeleton, cell adhesion to ECM and some cells, engage in in/out and out/in signaling.
What ligands do integrins bind to?
B1; alpha 1, 2: collagens and laminin
Alpha 3: fribronectin, laminin
Alpha 4: fibronectin, VCAM-1
Alpha 5: fibronectin
Alpha v: fibronectin, vitronectin
Cyclin D is associated with Kinase ___ and _____, functioning to put cell through ____ and ____ checkpoints
Kinases: CDK4 and CDK6
G1 and S
What does a tight junction (occluden) do?
Seals neighboring cells together in an epithelial sheet to prevent leakage
What do Zona adherens do?
Joins actin bundle in one cell, similar bundle in neighboring cell
What does a desmosome do?
Joins intermediate filaments in one cell to those of a neighbor
What does a gap junction do?
Forms channels to allow small molecules to pass cell to cell
What does a hemi desmosome do?
Anchors intermediate filaments to basil lamina
Zona = what kind of junctions
Tight and adherens
Macula= what kind of junctions
Desmosomes and hemidesmosome
What is the function of a tight junction?
Provides physical barrier to passage between cells, homophilic binding of claudins and occludens, prevents diffusion of membrane proteins
What is the function of adherens?
Cadherin mediated, calcium, dependent binding, invagination of epithelial sheets
Desmosome function
Anchoring Junction,cadherin mediated, calcium binding, homophilic
Many together impart great tensile strength to epithelial cells
Cytoskeletal elements include desmoplakin, plakoglobin, and plakophilin
Intermediate filaments attached to actin-spectrin intracellular plaque
Hemidesmosome function
Attaches to basal lamina, made of internal plaque on basal membrane
Gap junction functions
Connexon homophilic binding, pas ions and small molecules, hated channels (calcium, pH, secondary messenger)
What are process protrusions
Motile structures that constantly move towards/away from chemical gradients
What is chemotaxis
Cell process with migration in response to chemical gradient, moving towards higher concentrations
Gacher Disease Lysosomal Storage Disease
Defect in beta glucocerebrosidase
Abnormal endo and exocytosis
Functions of caveolae
Phagocytosis
Large vesicles are engulfed and trafficked elsewhere (ex: to lysosomes to be digested)
Endocytosis steps
Vesicle - early endosome - late endosome - lysosome
* golgi can also send vesicles to early endosome
Chemoreceptor arrays
- hexagonal structure
- sense and respond to chemical cues
Exocytosis steps
ER - golgi- extracellular space
Lysosome enzymes and function
- has ATPase pump proton pump to decrease pH
- opposite of its function in the mitochondria
Enzymes: nuclease, protease, lipase, phosphatase, glycolase etc
Autophagy
Autophagosomes activate in starved cells
Nucleus theories of origin and what is it made of?
Theories of origin:
Endosymbiotic theory
Protonucleus from viral cell
Made of euchromatin (11nm loosely packed inside, light in color) and heterochromatin (30nm tightly packed DNA, dark in color)
Where does mRNA exit nucleus?
Through nuclear pores
Nuclear lamina
- made of intermediate filaments
- dissolves during cell cycle
- made of heterochromatin
Nucleous functions
- made of fibrillar center, dense fibrillar and granular components
- largest amount of RNA polymerization
- MAKES RIBOSOMES
- adopter proteins used to make liquid-phase celebrations
What cell types under go what type of division?
Labile cells: constant division
Stable cells: under go re entry
Permanent cells: don't divide (neurons and cardiac cells)
What is cyclosporine
An immunosuppressant given to transplant patients
How long is each check point in the cell cycle in hours
G1: 5
S: 7
G2: 3
M: 1
G0: no division
What questions does G1 ask?
Is the environment favorable
What question does G2 ask?
Is the DNA replicated? Is the DNA repaired?
G1/S Control via p53 steps
1. Damaged DNA is arrested in G1
2. Protein kinases phosphorylate p53
3. p21 is transcribed after p53 binds
4. p21 (CDKI) is produced
5. p21 binds to G1-CDK and S-CDK and inactivates them
6. Cell cycle arrests in G1
7. Cell DNA is repaired or undergoes apoptosis
Rb gene mutations cause
Malignancies
___ and ____ prevent that cell from entering S phase
Rb and E2F
Rb is _____-phosphorylated by _____ which release E2F which transitions cells to S phase
Hypo
cyclin and CDK
What portion of the cell cycle does Rb and E2F regulate? What are Rb and E2F?
G1 and S transition
Rb= retinoblastoma protein, acts as tumor suppressor to prevent uncontrolled cell division
E2F= group of transcription factors that activate genes involved in cell cycle progression
Why don't elephants get cancer as easily?
They have more copies of the p53 gene and extra LIF genes that respond to DNA damage
p16 tumor suppressor genes specially inhibit ______ which prevents _______, which halts the cell cycle
CDK 4 and 6
Rb phosphorylation
What happens when p16 is turned off
Cancer
What are mitogens and what do they do?
They are signaling molecules that stimulate division
- trigger cell replication
- trigger mitosis
- act as growth factor
Only ___% of all cancer is diagnosed annually, which is approximately ____ cases.
3%
54,000
What cell changes cause an oral squamous cell carcinoma?
Increased mitogen, cyclin D1
Decreased p16, p53, Rb
Prophase I (Meiosis)
- chromosomes condense
- synaptonemal forms (breaks after pro 1)
-Chiasma holds crossed chromosomes together
Cohesion proteins keep _______ together across entire length
Sister chromatids
Metaphase I (Meiosis)
homologous pairs (tetrads) align at the equatorial plane and each pair attaches to a separate spindle fiber at the kinetochore
Prometaphase I (Meiosis)
the nuclear envelope breaks down and the meiotic spindles attach to kinetochores on chromosomes
Anaphase I (Meiosis)
Homologous chromosomes separate and sister chromatids remain attached
Chiasma breaks down
Telophase I (Meiosis)
chromosomes arrive at the spindle poles
Prophase II
Chromosomes condense
Metaphase II (Stage 7)
Paired chromatids line up in the middle