Download III. Exam Section III Intercellular Communication 1. Review of

III. Exam Section III
A. Intercellular Communication
1. Review of signaling system organization
a. Basic Ideas
1. Communications between two cells in a multicellular organism
2. Four components to all signaling systems
b. Ligands and their sources
1. Fluid dispersed: Endocrine, Paracrine, Synaptic, Cytosol Exchange
2. Iimmobilized ligands: Cell-to-cell signals, Matrix-to-cell signals
c. Receptors, second messenger cascades and target mechanisms
1. Transmembrane plasmamembrane receptors
2. Intracellular receptors
3. Intracellular second messenger cascades
4. One or more target mechanisms
2. Consensus signal pathways and molecules (Chapter 15)
a. Classic signal transduction pathways
1. G-protein linked receptor --- G-protein --- adenyl cyclase
2. G-protein linked receptor --- G-protein --- phospholipase C
3. Receptor tyrosine kinase --- ras --- MAPK
4. Receptor serine-threonine kinase --- SMAD --- gli protein
5. Cytokine receptor --- JAK --- STAT
6. Inhibitor inhibition pathways: Hedgehog, Wnt, thrombin-PPAR
7. Multicellularity and cell communication evolved independently in
plants and animals
3. Signal pathway structure depends on desired function; Example: muscle
contraction
a. The contractile filaments of all muscle types are organized in much the same
way but all come from different genes
b. Contractile regulation of skeletal muscle is designed to produce voluntary, allor-nothing contractions of great power but subject to fatigability
c. Contractile regulation of cardiac muscle is designed to produce involuntary, allor-nothing contractions of moderate power but not subject to fatigability
d. Contractile regulation of smooth muscle is designed to produce involuntary,
continuum contractions of low power but not subject to fatigability
e. How might the waving of cilia and flagella be similar
4. Integration, heirarchy and regulation by multiple required signals (Chapter 15)
a. Specialization in the ligand-receptor interaction
1. Specialization: Ligand-Receptor affinity and rate of turnover
2. Integration: Cells are exposed to hundreds of signals but gene
expression hardwires them to respond to a subset of signals
b. Single target mechanism pathways and convergent crosstalk
1. When a hardwired target mechanism is achieved in absence of ligand
2. Convergent, or redundant, cross-talk for essential responses occurs
when two or more ligands can produce the same target mechanism
c. Multiple target mechanism pathways and divergent crosstalk
1. Divergent cross-talk for complex, integrated responses where a single
ligand can activate two or more systems
d. Many complex functions vary by the combinations of signals present
1. Types of actions include neuron action potentials, cell division and
immune cell activation
2. Mechanisms of action include summation of ion movements at
plasmamembrane, transcription factor expression in the nucleus and
combined cytosolic and nuclear activation
3. Multiple signals also subject to heirarchical considerations/relationships
B. Control of Cell Number
1. Review of the mitotic cell cycle and cell death (Chapter 17, 18)
a. Cell number is a combination of cell division and cell death
b. Prokaryotic cells divide by binary fission
1. Circular DNA is copied and separate to opposite poles
2. Cell separates into two daughter cells
c. Certain protists have mechanism intermediate between binary fission and
mitosis
d. Eukaryotic cell cycle is divided into four phases
1. Gap 1: necessary to allow more time for growth after the previous cell
division and to prepare for DNA synthesis
2. Synthesis: DNA synthesis occurs
3. Gap 2: necessary to prepare for cell division
4. Cell Division: mitosis and cytokinesis
2. Regulation of cell number and quality during mitosis (Chapter 17, 18)
a. Review
1. Cell receives signal to: survive, grow and divide, differentiate, or die
2. If told to divide
a. Interphase: Gap 1, Synthesis, Gap 2
b. Mitotic cell division (or M phase): prophase, metaphase,
anaphase, telophase, and cytokinesis
b. Regulation
1. Four major checkpoints that regulate progression through cell cycle
a. G1/S checkpoint – to enter the cycle or not
b. S-checkpoint – to synthesize DNA or not
c. G2/M checkpoint – to divide the cell or not
d. M-checkpoint – to shift from metaphase to anaphase
2. Cell in G1 can either “go” or switch into nondividing state called G0
phase
a. Stop and Go regulation at the G1 checkpoint
3. Cyclins and Cyclin-dependent kinases control cell cycle checkpoints
a. Cychins are expressed and degraded; when present, the cell
moves forward
b. Cyclin-dependent kinases (Cdks) are always present and are
activated by the binding of their appropriate cyclin
4. What does cyclin:cdk phosphorylate?
a. G1-cdk phosphorylates Rb protein, in turn, loses inhibition of
E2F
b. M-cdk phosphorylates histones , lamins , and myosin
5. What happens when something goes wrong?
a. Internal activation of apoptosis = Intrinsic apoptotic pathway
i. Caused by DNA mutations
ii. Checkpoint arrest
b. External activation of apopotosis = Extrinsic apoptotic pathway
i. Caused external signaling
c. Activation of Caspase Cascade
d. Characteristics include cessation of DNA repair mechanisms,
cell shrinkage, nuclear membrane blebbing, DNA fragmentation,
and death
3. Regulation of cell type during cell division (Chapter 17, 22)
a. Review
1. Symmetric vs. asymmetric cell division
a. Commonly both daughter cells are just like parent cell
b. In many differentiation events both daughters are not like parent
c. In specialized stem cell differentiations one daughter cell is like
the parent cell, while the other is different
2. Stem cell and embryonic cell divisions
a. Cells that divide in the adult
b. Embryonic cell divisions and differentiations
c. Cancer: dedifferentiation or stem cell mutation?
b. Regulation
1. Control in the cytosol
a. G2 phase development across the cleavage plane
b. The specialized case of embryonic cleavage
2. Control in the nucleus
a. Gene availability, euchromatin and heterochromatin structure
b. Transcription factors, SNuRPs and other regulators