Unit 5: Cell Division and Cell Signalling

1. Mitosis

Mitosis is a type of cell division that results in two daughter cells each having the same number and kind of chromosomes as the parent nucleus. It is used for growth and repair in somatic (body) cells.

Result: 1 Diploid (2n) Cell → 2 Genetically Identical Diploid (2n) Cells

Phases of Mitosis (PMAT)

1. Prophase:
   • Chromatin condenses to form visible chromosomes (each with two sister chromatids joined at a centromere).
   • The nucleolus disappears.
   • The mitotic spindle (made of microtubules) begins to form from the centrosomes.
   • The nuclear envelope breaks down.
2. Metaphase:
   • The chromosomes, now fully condensed, line up at the metaphase plate (an imaginary plane at the cell's equator).
   • Spindle fibers (microtubules) from opposite poles attach to the kinetochores (protein structures at the centromere) of each chromosome.
3. Anaphase:
   • The centromeres split.
   • The sister chromatids separate and are pulled to opposite poles of the cell by the shortening spindle fibers.
   • Each chromatid is now considered an individual chromosome.
4. Telophase:
   • The chromosomes arrive at the poles and begin to decondense back into chromatin.
   • New nuclear envelopes form around the two sets of chromosomes.
   • The nucleoli reappear.
   • The mitotic spindle breaks down.

Cytokinesis: The division of the cytoplasm, which usually begins during late anaphase or telophase. In animal cells, it occurs via a cleavage furrow.

2. Meiosis

Meiosis is a special type of cell division of germ (sex) cells to produce gametes (like sperm and egg cells). It involves two rounds of division, resulting in four daughter cells with half the number of chromosomes as the parent cell.

Result: 1 Diploid (2n) Cell → 4 Genetically Different Haploid (n) Cells

Meiosis I (Reductional Division)

This is where homologous chromosomes are separated.

• Prophase I: The most complex phase.
  • Homologous chromosomes pair up (synapsis) to form bivalents (or tetrads).
  • Crossing Over occurs: Non-sister chromatids of a homologous pair exchange genetic material. This creates new gene combinations and is a major source of genetic variation.
• Metaphase I: Homologous pairs (bivalents) line up at the metaphase plate.
• Anaphase I: Homologous chromosomes separate and are pulled to opposite poles. (Sister chromatids remain attached).
• Telophase I & Cytokinesis: Two haploid cells are formed, but each chromosome still has two chromatids.

Meiosis II (Equational Division)

This phase is mechanically identical to mitosis. Sister chromatids are separated.

• Prophase II: Spindle forms.
• Metaphase II: Individual chromosomes (with two chromatids) line up at the metaphase plate.
• Anaphase II: Sister chromatids separate and move to opposite poles.
• Telophase II & Cytokinesis: Four haploid daughter cells are formed, each with a single set of unreplicated chromosomes.

3. Cell Cycle and its Regulation

The Cell Cycle

The cell cycle is the ordered series of events that a cell goes through from its formation until its own division.

• Interphase (The "growing" phase): The longest part of the cycle.
  • G1 (Gap 1) Phase: The cell grows in size, synthesizes proteins, and carries out its normal metabolic functions.
  • S (Synthesis) Phase: DNA replication occurs. The cell's chromosomes are duplicated.
  • G2 (Gap 2) Phase: The cell continues to grow and makes final preparations for division (e.g., synthesizes proteins for mitosis).
• M (Mitotic) Phase:
  • Mitosis: Nuclear division (as described above).
  • Cytokinesis: Cytoplasmic division.

Cell Cycle Regulation

The cell cycle is not automatic; it is tightly controlled by a molecular control system involving checkpoints, cyclins, and Cdks.

• Checkpoints: "Stop" signals that pause the cycle to ensure all processes have been completed correctly before proceeding.
  • G1 Checkpoint ("Restriction Point"): The most important. Checks for cell size, nutrients, and growth factors. If it passes, it's committed to divide.
  • G2 Checkpoint: Checks if DNA replication (S phase) is complete and if any DNA is damaged.
  • M (Spindle) Checkpoint: Checks if all chromosomes are properly attached to the mitotic spindle at the metaphase plate.
• Key Regulatory Molecules:
  • Cyclins: A family of proteins whose concentration cycles up and down during the cell cycle. They act as activators.
  • Cyclin-Dependent Kinases (Cdks): A family of enzymes (kinases) that, when activated by binding to a cyclin, phosphorylate (add a phosphate to) other proteins to drive the cell cycle forward.

How it works (Simplified): A cyclin (e.g., Mitotic Cyclin) builds up during G2. It binds to its Cdk partner, forming an active complex (e.g., MPF - Maturation Promoting Factor). This complex then phosphorylates proteins that trigger the events of mitosis (like nuclear envelope breakdown).

4. GPCR (G Protein-Coupled Receptor)

Cell signaling is how cells communicate with each other. GPCRs are a large family of cell surface receptors that are involved in many physiological processes (e.g., vision, smell, hormone responses).

Mechanism of GPCR Signaling:

1. Reception: A signaling molecule (first messenger, e.g., a hormone like adrenaline) binds to the specific GPCR on the outside of the cell.
2. Activation: This binding causes the GPCR to change shape, which in turn activates an associated G Protein on the inner side of the membrane. The G protein "activates" by exchanging its bound GDP (inactive) for a GTP (active).
3. Transduction: The activated G protein (now with GTP) splits and moves along the membrane to bind to and activate an effector enzyme (e.g., Adenylyl Cyclase).
4. Response: The effector enzyme then triggers the next step in the pathway, often by producing a second messenger.

5. Role of Second Messenger (cAMP)

The first messenger (like the hormone) is the signal *outside* the cell. Second messengers are small, non-protein, water-soluble molecules or ions *inside* the cell that relay and amplify the signal.

cAMP as a Second Messenger

Cyclic AMP (cAMP) is one of the most common second messengers.

The cAMP Pathway (A continuation of the GPCR example):

1. The activated G protein (from step 3 above) binds to and activates the effector enzyme, Adenylyl Cyclase.
2. Adenylyl Cyclase converts ATP into cAMP.
3. The now-abundant cAMP (the second messenger) diffuses through the cytoplasm.
4. cAMP's main target is Protein Kinase A (PKA). Binding of cAMP activates PKA.
5. The activated PKA (a kinase) then phosphorylates various other proteins in the cell, activating or deactivating them.
6. This phosphorylation cascade leads to the final cellular response (e.g., in the case of adrenaline, PKA activates enzymes that break down glycogen into glucose for energy).