Cell Signaling, Cell Cycle, Mitosis/ Meiosis, Mendelian Genetics

Unit 4, BIO 221 lecture

Why do cells communicate?

Nutrients, Temperature, pH, osmotic conditions, light, and oxygen availability

Cell Membrane receptors

Most are intermembrane proteins. Cell surface receptors. 3 Parts; extracellular domain detects signals, Cytoplasmic/ intercellular domain, produces an internal signal, Transmembrane domain, allows the receptor to stay embedded into the bilayer.

Signal Transduction cascade

Specific signaling molecule or environmental stimulus

What are the 3 Cell responses?

Differential Gene expression, changing enzyme activity, changing cell shape or movement

Differential Gene Expression

Activation/ deactivation of specific genes

Changing Enzyme Activity

Alters metabolism or other cell functions

Changing Cell Shape or Movement

Affects structural proteins

Types of Cell Communication

Gap Junction, Contact-Dependent Signaling, Autocrine Signaling, Paracrine Signaling, Endocrine Signaling

Gap Junctions

Direct Cell to Cell communication via transfer of small molecules

Contact-Dependent Signaling

Signal: Membrane of cell #1

Receptor: On membrane of cell #2

Autocrine Signaling

Signal: Secreted by cell #1

Receptors: Other cells and cell #1

Paracrine Signaling

Signal: secreted by cell #1

Receptors: Other cells but not the cell that produced the signal

Endocrine Signaling

Hormones

Signal: Cell or Cells that secrete (AKA Glands)

Receptors: Long distance away

Cell Responses

1. Changes in enzyme activity

2. Changes in structural proteins

3. Changes in gene expression - Altering the activity of transcription factors

Stages of Cell Signaling

Receptor Activation

• The Binding of a signaling molecules causes a conformational change in a receptor that activates Its function

Signal Transduction

• The activated receptor stimulates a series of proteins that forms a signal transduction pathway

Cellular Response

• The signal transduction pathway affects the functions and/ or amounts of cellular proteins, thereby producing a cellular response

3 Basic Types of Cell Surface Receptors

Enzyme-linked receptors 

• Binding of ligand (signaling molecule) activates catalytic domain of the receptor 

• Cytoplasmic domain functions as an enzyme 

  • Enzyme: protein kinases 

• The receptor itself is the enzyme 

G-protein coupled receptors 

• Binding of ligand activates a G-protein 

• Cytoplasmic domain acts as a guanine-nucleotide exchange factor (GEF) 

  • GEF attached GTP to a G-protein 

    • That attachment activates the G-protein 

Ligand-gated ion channels 

• Binding of ligand opens gated channel 

G-Protein Coupled Receptors

Act as GEFs, activate G-proteins 

• G-proteins are membrane associated proteins 

• Often lipid anchored 

• Made of 3 subunits 

  • Alpha 

    • Binds the GTP 

  • Beta 

  • Gamma 

• Signal that binds the GPCR -> GEF activity -> activates G-protein 

• Disassociates the alpha subunit from the beta and alpha subunit 

• Signal transduction occurs 

Nuclear Receptors

Bind to hormones 

• Estrogen – steroid lipid 

  • Estrogen diffuses across the plasma membrane, enters the nucleus, and binds to the estrogen receptors. The receptors undergo a conformational change. 

  • Estrogen receptors form a dimer, bind next to specific genes, and activate their transcription. The mRNAs are then translated into proteins that affect the structure of the cell. 

What is Cytogenetics

The study of the structure and function of chromosomes

Ploidy

The number of sets of chromosomes in a cell, or in the cells of an organism

• diploid

  • 2 sets of chromosomes

• haploid

  • Haploid refers to a cell that contains a single set of chromosomes, typically used in sexual reproduction.

• others

Cell Cycle Stages and Processes

G1 phase: growth 

• 6 chromosomes total, 3 pairs 

S phase: synthesis phase (replication occurs) 

• Replication occurs, each chromosome is replicated to create 2 sets 

G2 Growth 

• Preparation for mitosis 

Mitosis

The process of cell division that results in two identicle daughter cells.

G1: Cell growth, preparation for cell division 

• G1 restriction: Checkpoint to determine if cell division should occur 

  • Size, contact, chromosome integrity (G0) 

S Phase: DNA replication – DNA content doubles, but not chromosome number 

• Replicated Chromosomes consist of sister chromatids. 

G2: preparation for M phase 

• G2 checkpoint 

3 Key checkpoints 

• G1: G1 -> S 

  • Checks for: 

  •  DNA damage 

  • Enough nutrients 

  • Presence of growth cues 

    • If something is wrong, the cell will not continue to S phase 

• G2 

  •  Check for DNA damage 

  • Check for full DNA replication 

• M – during mitosis/ metaphase 

  • Cell is checking whether the sister chromatids are connected correctly to the microtubules

Centromere

Center of a chromosome where both sister chromatid touch.

Kinetochore

• complex protein structure at centromere region

What 2 families of proteins control checkpoints

• Cyclin dependent kinases (CDKs) 

  • Phosphorylates target proteins have a role in advancing cell cycle 

  • Kinase activity is dependent on binding with a cyclin 

• Cyclins – levels rise + fall with the cell cycle 

G1 Checkpoint

• Cyclin E + CDK 2 

  • This triggers the cell into S phase is everything is good to continue 

• E2F – a transcription factor that regulates genes required for S-phase 

  • Function by blocked RB (seen on slide 11 of Cell Cycle and mitosis + meiosis) 

  • RB is phosphorylated by and active CDK2 

  • RB releases E2F 

  • E2F then activates S-phase genes 

What does the P53 Protein do?

• blocks the cell cycle

• DNA damage

• If DNA is damaged, then P53 accumulates in the cell and signals for the cell to either repair the DNA or if repair cannot be done, apoptosis occurs