BIOL 111 Chapter 18

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Cell Communication and Signaling

Signals need to make their way into DNA in order to have effect on cell function/behavior

External Signals: Local (signaling cell affects cells around it) or Long-distance (signaling cell is far away from target cell)

Signal molecule types: protein, lipid, ion, carbohydrate

Highly conserved: signaling systems are identical across most of all life on earth. (evidence for evolutionary relatedness)

Methods

Signal Transduction Pathway

Reception

1. Signal molecule binds to receptor protein

Transduction

1. Receptor protein is altered
2. Other relay molecules respond to receptor
3. Chain reaction continues down signal transduction pathway

Response

1. Activation/Repression of genes
2. Rearrange cytoskeleton
3. Cell migration
4. Enzyme activation

Gene Regulation

Controlling whether genes are expressed or suppressed

Chromatine Structure alteration

8 histone proteins + DNA = nucleosome

Results in 2 types of modifications:

Histone modification

Add acetyl groups (–(C=0)–CH₃) to loosen DNA

Add methyl groups (–CH₃) to condense

DNA modification

Add Methyl groups to certain bases (usually deactivates genes)

Resulting modifications inherited in all descendent cells

Regulation of transcription process

Review: Anatomy of a Gene

• Enhancers — DNA sequence where cell-type specific Transcription Factors (TF) bind
• Promoter — DNA sequence where General TFs bind
• Termination — DNA sequence where RNA Polymerase stops

Activating Genes

Figure 18.9: A model for the action of enhancers and transcription activators

Specific TFs (activators) bind to enhancers and interact with mediator proteins

General TFs bind to promoters and interact with RNA polymerase and mediator proteins

DNA-bending proteins bend the DNA to bring enhancers and promoters together

The interactions between all these proteins control how RNA polymerase works

Terminology

Genomic equivalence

Cells in organism have exact same DNA

Differential gene expression

Different genes expressed in different cells

For example, in liver cell, only certain activators are available, so gene for crystallin (makes lens clear) is not expressed. Vice versa in lens cell in eye

Regulation After transcript

Controllable factors:

1. Alternate RNA splicing
2. RNA Degradation: "lifespan" of mRNA (length of poly-A tail
3. Inhibition of Translation (blocking ribosome for some time)
4. Protein Processing: some proteins need to be cut smaller or lengthened
5. Protein Degradation: "lifespan" of Protein (Ubiquitin "marks" protein for destruction)

Tuesday, November 30, 2010

Gene Expression Regulation

Regulatory RNA

We've already studied the following RNA structures:

• mRNA — Codes for Proteins
• tRNA — Brings Amino Acids to Ribosome and matches to mRNA
• rRNA — Makes part of Ribosome
• snRNA — Aids in splicing process of mRNA

New RNA structure: miRNA — controls "lifespan" of mRNA.

Mechanics

1. Primary miRNA transcript structure folds back on itself.
2. A dicer protein trims small pieces (15-30 base pairs) from folded transcript.
3. miRNA binds with protein to form miRNA-protein complex
4. miRNA binds to the complimentary mRNA
   1. Complete match signals mRNA degradation
   2. Partial match signals prevention of mRNA translation

Gene Expression During Development

Developmental Biology: How does a single fertilized cell grow and develop into an adult? How is this affected by Gene regulation

Zygote → Blastula → Gastrula → All different cells in body

Product of #Genomic Equivalence and #Differential Gene Expression

Gamete contributions

Sperm

Haploid genome

Centrosomes

Imprinted Genes (stimulate growth)

Egg

Haploid genome

Mitochondria

Cytoplasm (other organelles and cytosol)

Imprinted Genes (equalize growth)

Cytoplasmic determinants signals that influence early patterning in embryo.

Cytoplasmic Determinants

Uneven distribution: when cell divides, one cell gets more of a certain type of cytoplasmic determinants

Other Signals

• neighboring cells
• chemicals in surrounding aqueous solution

Cell Differentiation

1. Cell Receives Signal
2. Signal activates regulatory genes (Determination Stage - cells determine what they will become)
3. Regulatory genes activate cell-type-specific factors (Differentiated Stage - specialized structure and function)

Example: Muscle Cell

Embryonic precursor cell: Master regulatory gene for myoD is OFF

Determined Myoblast mucscle cell: regulatory gene for myoD is turned on; myoD protein produced; that protein activates more transcription factor proteins, which then activates more

Result is Differentiated muscle cell

Pattern Formation

How do certain cells form where they need to?

Body Axes: (3D Structure)

• anterior/posterior (head/tail)
• dorsal/ventral (back/belly)
• left/right

Organ/appendage fields form in given quadrants due to concentration gradients of certain proteins

Example: Drysophila

Anterior head, thorax, posterior abdomen; dorsal left/right wings, ventral left right legs

Mutations

Hox gene mutants (disrupts organ/appendage fields)

Legs grow out of fly's head "Antennapedia"

Bioid gene mutants (disrupts anterior/posterior formation)

Just one big posterior... no anterior region

Gene (Un)Regulation During Cancer

Cancer is defined as unregulated cell growth.

Occurs when cell undergoes several mutations due to (combination of)

• radiation
• chemicals
• heredity

Terminology

Proto-oncogene

A normal, wild-type gene that functions in cell growth or cell division

Oncogene

A mutated version of a proto-oncogene that results in unregulated cell growth/division

Tumor-suppressor gene

A normal gene that is a part of the cell's defense against unregulated cell growth/division

Alternations in gene regulation

1. Translocation of a gene (excess proteins)
2. Gene duplication (excess proteins)
3. Mutation in a gene or control element (creates degradation-resistant protein)
4. Over-production of cell cycle stimulant
5. No production of cell cycle inhibitor (defective inhibitor proteins)

Multistep model for cancer development

1. Individual undergoes multiple genetic changes (some inherited; others aquired)
2. If enough cancer genes are activated, a tumor forms and grows
3. Malignant tumors start affecting other cells around them
4. Metastasized tumors move around and affect cells throughout your body