Cell Signaling Animal cells communicate by: Direct contact (gap junctions) Secreting local regulators (growth factors, neurotransmitters) Long distance (hormones)

3 Stages of Cell Signaling: Reception: Detection of a signal molecule (ligand) coming from outside the cell Transduction: Convert signal to a form that can bring about a cellular response Response: Cellular response to the signal molecule

1. Reception Binding between signal molecule (ligand) + receptor is highly specific. Receptors found in: Intracellular receptors (cytoplasm, nucleus) hydrophobic or small Eg. testosterone or nitric oxide (NO) Plasma membrane receptor water-soluble ligands

Plasma Membrane Receptors G-Protein Coupled Receptor (GPCR) Tyrosine Kinase Ligand-Gated Ion Channels 7 transmembrane segments in membrane Attaches (P) to tyrosine Signal on receptor changes shape G protein + GTP activates enzyme  cell response Activate multiple cellular 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  G2  mitosis  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 Checkpoints 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 G2 checkpoint M Phase checkpoint Anaphase does not begin unless chromatids are properly attached to spindle at metaphase plate

G1 Checkpoint

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

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

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

Asexual vs. sexual reproduction

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

Zygote divides by mitosis to make multicellular diploid organism 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

Varieties of Sexual Life Cycles

Human Life Cycle

Animals

Alternation of Generations Plant and some algae Sporophyte (2n): makes haploid spores by meiosis Spore  gametophyte by mitosis Gametophyte (n): makes haploid gametes by mitosis

Fungi, protists, algae

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 replicated Prophase I: Synapsis: homologous chromosomes pair up Tetrad = 4 sister chromatids Crossing over at the chiasmata Metaphase I: Tetrads line up Anaphase 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