Cell Signaling

Animal cells communicate by:

• Direct contact (gap junctions)

• Secreting local regulators (growth factors, neurotransmitters)

• Long distance (hormones)

3 Stages of Cell Signaling:

1. Reception: Detection of a signal molecule (ligand) coming from outside the cell

2. Transduction: Convert signal to a form that can bring about a cellular response

3. Response: Cellular response to the signal molecule

1. Reception

• Binding between signal molecule (ligand) + receptor is highly specific.

• Receptors found in:a) Intracellular receptors (cytoplasm, nucleus) hydrophobic or small Eg. testosterone or nitric oxide (NO)

b) Plasma membrane receptor• water-soluble ligands

Plasma Membrane Receptors

G-Protein Coupled Receptor (GPCR)

Tyrosine KinaseLigand-Gated Ion

Channels

7 transmembranesegments in membrane

Attaches (P) to tyrosine

Signal on receptor changes shape

G protein + GTP activates enzyme cell response

Activate multiplecellular responses

at once

Regulate flow of specific ions(Ca2+, Na+)

G-Protein-Coupled Receptor

Receptor Tyrosine Kinase

Ligand-Gated Ion Channel

2. Transduction

• Cascades of molecular interactions relay signals from receptors target molecules

• Protein kinase: enzyme that phosphorylates and activates proteins at next level

• Phosphorylation cascade: enhance and amplify signal

Second Messengers• small, nonprotein molecules/ions that can relay

signal inside cell– Eg. cyclic AMP (cAMP) and Ca2+

3. Response

• Regulate protein synthesis by turning on/off genes in nucleus (gene expression)

• Regulate activity of proteins in cytoplasm

Apoptosis = cell suicide

• Cell is dismantled and digested

• Triggered by signals that activate cascade of “suicide” proteins (caspase)

– Protect neighboring cells from damage

– Animal development & maintenance

Cell Cycle: life of a cell from its formation until it divides

Functions of Cell Division: Reproduction, Growth and Tissue Renewal

Genome = all of a cell’s genetic info (DNA)

Prokaryote: single, circular chromosome Eukaryote: more than one linear chromosomes

Eg. Human:46 chromosomes, mouse: 40, fruit fly: 8

Each chromosome must be duplicated before cell division

• Duplicated chromosome = 2 sister chromatids attached by a centromere

Somatic Cells Gametes• Body cells• diploid (2n): 2 of each

type of chromosome• Divide by mitosis

• Humans: 2n = 46

• Sex cells (sperm/egg)• Haploid (n): 1 of each

type of chromosome• Divide by meiosis

• Humans: n = 23

Phases of the Cell Cycle

Phases of the Cell Cycle• The mitotic phase alternates with interphase:

G1 S G2mitosis cytokinesis• Interphase (90% of cell cycle)

– G1 Phase: cell grows and carries out normal functions

– S Phase: duplicates chromosomes– G2 Phase: prepares for cell division

• M Phase (mitotic)– Mitosis: nucleus divides– Cytokinesis: cytoplasm divides

Mitosis: Prophase Prometaphase Metaphase

Anaphase Telophase

Mitosis

1. Prophase– Chromatin fibers condense and coil– Nucleoli disappear– Spindle (microtubules) begins to form– Centrosomes begin to move to opposite ends

2. Prometaphase– Nuclear envelope fragments– Microtubules invade nucleus– Kinetochores attach to microtubules

Prophase & Prometaphase

Mitotic spindle at metaphase

Kinetochore = proteins associated with DNA at centromere

3. Metaphase– Chromosomes line up on metaphase plate at

equator– Centrioles are at opposite poles (ends)

4. Anaphase (shortest phase)– Chromatids separate and pulled apart by motor

proteins toward opposite ends of cell– Chromatids are called chromosomes now– Cell elongates

Metaphase & Anaphase

5. Telophase– Nuclear membrane re-forms around chromosomes– Chromosomes less condensed

Cytokinesis– Cytoplasm of cell divided– Animal Cells: cleavage furrow– Plant Cells: cell plate forms

Cytokinesis in animal vs. plant cells

During anaphase• Chromosomes

walked to poles by motor proteins

• Kinetochore microtubules shorten at ends as they depolymerize

Bacterial cells divide by Binary Fission

Cell Cycle Control System• Checkpoint = control point where stop/go signals

regulate the cell cycle

Major Checkpoints1. G1 checkpoint (Most important!)

– “Go” completes whole cell cycle– “Stop” cell enters nondividing state (G0 Phase)

• Nerve, muscle cells stay at G0; liver cells called back from G0

2. G2 checkpoint3. M Phase checkpoint

– Anaphase does not begin unless chromatids are properly attached to spindle at metaphase plate

G1 Checkpoint

Internal Regulatory Molecules

1. Kinases (cyclin-dependent kinase, Cdk): protein enzyme controls cell cycle; active when connected to cyclin

2. Cyclins: proteins which attach to kinases (Cdk) to activate them; levels fluctuate in the cell cycle

3. MPF: maturation-promoting factor; specific Cdk which allows cells to pass G2 and go to M phase

External Regulatory Factors

Growth Factor: proteins released by other cells to stimulate cell division

Density-Dependent Inhibition: crowded cells normally stop dividing; cell-surface protein binds to adjoining cell to inhibit growth

Anchorage Dependence: cells must be attached to another cell or ECM to divide

External Regulatory Factors

Cancer Cells

Cancer: disorder in which cells lose the ability to control growth by not responding to regulation.

• multistep process of about 5-7 genetic changes (for a human) for a cell to transform

• loses anchorage dependency and density-dependency regulation

Normal Cells Cancer Cells

Tumors = mass of abnormal cells

• Benign tumor: lump of cells remain at original site

• Malignant tumor: invasive - impairs functions of 1+ organs (called cancer)

• Metastasis: cells separate from tumor and travel to other parts of body

Types of Reproduction

ASEXUAL

• Produces clones (genetically identical)

• Single parent

• Little variation in population - only through mutations

• Fast and energy efficient

• Eg. budding, binary fission

SEXUAL

• Meiosis produces gametes (sex cells)

• 2 parents: male/female

• Lots of variation/diversity

• Slower and energy consumptive

• Eg. humans, trees

Chromosomes• Somatic (body) cell: 2n = 46 chromosomes• Each pair of homologous chromosomes includes 1

chromosome from each parent• Autosomes: 22 pairs of chromosomes that do not

determine sex• Sex chromosomes: X and Y

• Females: XX• Males: XY

• Gametes (n=23): 22 autosomes + 1 sex chromosome• Egg: 22 + X• Sperm: 22 + X **or** 22 + Y

Homologous Chromosomes in a Somatic Cell

Karyotype: a picture of an organism’s complete set of

chromosomes

• Arranged from largest smallest pair

Life cycle: reproductive history of organism, from conception production of own offspring

• Fertilization and meiosis alternate in sexual life cycles

• Meiosis: cell division that reduces # of chromosomes (2n n), creates gametes

• Fertilization: combine gametes (sperm + egg)

– Fertilized egg = zygote (2n)

• Zygote divides by mitosis to make multicellular diploid organism

Human Life Cycle

Meiosis = reduction division Cells divide twice Result: 4 daughter cells,

each with half as many chromosomes as parent cell

Meiosis I (1st division)Interphase: chromosomes replicatedProphase I: Synapsis: homologous chromosomes pair up Tetrad = 4 sister chromatids Crossing over at the chiasmataMetaphase I: Tetrads line upAnaphase I: Pairs of homologous chromosomes separate (Sister chromatids still attached by centromere)Telophase I & Cytokinesis: Haploid set of chromosomes in each cell Each chromosome = 2 sister chromatids Some species: chromatin & nucleus reforms

Meiosis II (2nd division) = create gametes

Prophase II: No interphase No crossing over Spindle formsMetaphase II: Chromosomes line upAnaphase II: Sister chromatids separateTelophase II: 4 haploid cells Nuclei reappear Each daughter cell genetically unique

Events Unique to Meiosis I (not in mitosis)

1. Prophase I: Synapsis and crossing over

2. Metaphase I: pairs of homologous chromosomes line up on metaphase plate

3. Anaphase I: homologous pairs separate sister chromatids still attached at centromere

Sources of Genetic Variation:1. Crossing Over

– Exchange genetic material

– Recombinant chromosomes

Sources of Genetic Variation:2. Independent Assortment of Chromosomes

– Random orientation of homologous pairs in Metaphase I

Sources of Genetic Variation:3. Random Fertilization

– Any sperm + Any egg

– 8 million X 8 million = 64 trillion combinations!

Mitosis Meiosis

Both are divisions of cell nucleus

• Somatic cells

• 1 division

• 2 diploid daughter cells

• Clones

• From zygote to death

• Purpose: growth and repair

• No synapsis, crossing over

• Gametes

• 2 divisions

• 4 haploid daughter cells

• Genetically different-less than 1 in 8 million alike

• Females before birth follicles are formed. Mature ova released beginning puberty

• Purpose: Reproduction

MENDEL’S PRINCIPLES

1. Alternate version of genes (alleles) cause variations in inherited characteristics among offspring.

2. For each character, every organism inherits one allele from each parent.

3. If 2 alleles are different, the dominant allele will be fully expressed; the recessive allele will have no noticeable effect on offspring’s appearance.

4. Law of Segregation: the 2 alleles for each character separate during gamete formation.

• P (parental) generation = true breeding plants• F1 (first filial) generation = offspring • F2 (second filial) generation = F1 offspring

Alleles: alternate versions of a gene

7 characters in pea plants

Dominant vs. Recessive(expressed) or (hidden)

Law of Segregation

dominant (P), recessive (p)• homozygous = 2 same alleles (PP or pp)• heterozygous = 2 different alleles (Pp)

Phenotype: expressed physical traitsGenotype: genetic make-up

Testcross: determine if dominant trait is homozygous or heterozygous by crossing with

recessive (pp)

Law of Independent Assortment:Each pair of alleles segregates (separates) independently

during gamete formationEg. color is separate from shape

• Monohybrid cross: study 1 character– eg. flower color

• Dihybrid cross: study 2 characters– eg. flower color & seed shape

The laws of probability govern Mendelian inheritance

• Rule of Multiplication:– probability that 2+ independent events will occur

together in a specific combination multiply probabilities of each event

• Ex. 1: probability of throwing 2 sixes– 1/6 x 1/6 = 1/36

• Ex. 2: probability of having 5 boys in a row– ½ x ½ x ½ x ½ x ½ = 1/32

• Ex. 3: If cross AABbCc x AaBbCc, probability of offspring with AaBbcc is:– Answer: ½ x ½ x ¼ = 1/16

The laws of probability govern Mendelian inheritance

• Rule of Addition:– Probability that 2+ mutually exclusive events will

occur add together individual probabilities

• Ex. 1: chances of throwing a die that will land on 4 or 5?– 1/6 + 1/6 = 1/3

Extending Mendelian GeneticsThe relationship between genotype and phenotype is rarely simple

Complete Dominance: heterozygote and homozygote for dominant allele are indistinguishable• Eg. YY or Yy = yellow seed

Incomplete Dominance: F1

hybrids have appearance that is between that of 2 parents• Eg. red x white = pink flowers

Codominance: phenotype of both alleles is expressed• Eg. red hair x white hairs = roan horses

Multiple Alleles: gene has 2+ alleles• Eg. human ABO blood groups

• Alleles = IA, IB, i• IA,IB = Codominant

Blood Typing

Phenotype(Blood Group) Genotype(s)

Type A IAIA or IAi

Type B IBIB or IBi

Type AB IAIB

Type O ii

Blood Transfusions

• Blood transfusions must match blood type• Mixing of foreign blood clumping death

Pleiotropy: single gene has multiple phenotypic effects (Eg. sickle cell anemia)

Epistasis: one gene alters the phenotypic expression of another gene (eg. albinism - white fur color in mammals)

ee overrides the expression of all the B,b genotypes

Polygenic Inheritance: the effect of 2 or more genes acting upon a single phenotypic character (eg. skin color, height)

Nature and Nurture: both genetic and environmental factors influence phenotype

Hydrangea flowers vary in shade and intensity of color depending on acidity and aluminum content of the soil.

Mendelian Inheritance in Humans

Pedigree: diagram that shows the relationship between parents/offspring across 2+ generations

Woman = Man = Trait expressed:

Genetic Testing

May be used on a fetus to detect genetic disordersAmniocentesis: remove amniotic fluid around fetus to

culture for karyotypeChorionic villus sampling: insert narrow tube in cervix

to extract sample of placenta with fetal cells for karyotype

Sex-linked genes

• Sex-linked gene on X or Y• Females (XX), male (XY)

– Eggs = X, sperm = X or Y• Fathers pass X-linked genes to daughters, but not

sons• Males express recessive trait on the single X

(hemizygous)• Females can be affected or carrier

Transmission of sex-linked recessive traits

Sex-linked disorders: ColorblindnessDuchenne muscular dystrophyHemophilia

X-InactivationBarr body = inactive X chromosome; regulate gene dosage in females during embryonic development

• Cats: allele for fur color is on X

• Only female cats can be tortoiseshell or calico.

Human development• Y chromosome required for development of testes• Embryo gonads indifferent at 2 months• SRY gene: sex-determining region of Y• Codes for protein that regulates other genes

Genetic Recombination: production of offspring with new combo of genes from parents

• If offspring look like parents parental types• If different from parents recombinants

• If results do not follow Mendel’s Law of Independent Assortment, then the genes are probably linked

Linked genes: located on same chromosome and tend to be inherited together during cell division

Crossing over: explains why some linked genes get separated during meiosis

• the further apart 2 genes on same chromosome, the higher the probability of crossing over and the higher the recombination frequency

Calculating recombination frequency

Linkage Map: genetic map that is based on % of cross-over events

• 1 map unit = 1% recombination frequency• Express relative distances along chromosome• 50% recombination = far apart on same chromosome

or on 2 different chromosomes

Nondisjunction: chromosomes fail to separate properly in Meiosis I or Meiosis II

Nondisjunction

• Aneuploidy: incorrect # chromosomes

– Monosomy (1 copy) or Trisomy (3 copies)

• Polyploidy: 2+ complete sets of chromosomes; 3n or 4n

– Rare in animals, frequent in plants

A tetraploid mammal. Scientists think this species may have arisen when an ancestor doubled its chromosome # by errors in mitosis or meiosis.

Chromosomal Mutations

Chromosomal Mutations

Exceptions to Mendelian inheritance• Genomic imprinting: phenotypic effect of gene

depends on whether from M or F parent• Silence genes by adding methyl groups to DNA

(methylation)

Exceptions to Mendelian inheritance

• Some genes located in organelles– Mitochondria, chloroplasts,

plastids– Contain small circular DNA

• Mitochondria = maternal inheritance (eggs)

Variegated (striped or spotted) leaves result from mutations in pigment genes in plastids, which generally are inherited from

the maternal parent.