(a) What is cell cycle ? Draw an overview of molecular events during cell cycle. Discuss the role of protein kinases in the…

(a) Cell cycle, its molecular events and protein kinases in the meiotic cycle

The cell cycle is the ordered sequence of events by which a cell duplicates its contents and divides: interphase (G₁, S, G₂) followed by M phase. Progress is driven by cyclin-dependent kinases (CDKs) activated by cyclins whose levels oscillate, and is guarded by checkpoints (G₁/S, G₂/M and the spindle assembly checkpoint).

Overview of molecular events (diagram below):

• G₁: cyclin D–CDK4/6 phosphorylates Rb, releasing E2F, which switches on S-phase genes.
• G₁/S: cyclin E–CDK2 triggers firing of the replication origins.
• S: cyclin A–CDK2 supports DNA replication, which happens once only.
• G₂/M: cyclin B–CDK1 (MPF) is held inactive by Wee1 (phosphorylation of Thr14 and Tyr15) until Cdc25 phosphatase removes these phosphates.
• M: active MPF drives nuclear envelope breakdown, chromosome condensation and spindle formation; the APC/C then destroys cyclin B and securin, so anaphase and exit from mitosis follow.

Meiotic cycle. Oocytes are arrested in prophase I with inactive CDK1–cyclin B. A hormonal signal (progesterone in frogs, LH in mammals) lowers cAMP and PKA activity, activating Cdc25 and inactivating Wee1/Myt1, so MPF is activated and the oocyte enters meiosis I (germinal vesicle breakdown). The Mos–MAPK pathway is activated, helps to organise the spindle, and Aurora and Polo kinases act in spindle and kinetochore function. After meiosis I, cyclin B is only partly degraded by the APC/C and S phase is skipped, so MPF rises again and meiosis II begins. In vertebrates the egg then arrests in metaphase II through cytostatic factor (Mos–MAPK, Emi2), which inhibits the APC/C. Fertilisation raises calcium, which activates CaMKII, so Emi2 is destroyed, cyclin B is degraded and the egg completes meiosis II.

(b) Polymorphism and the dynamic system of lysosomes

Lysosomes are membrane-bound organelles with acid hydrolases (about 50 types, working at pH 4.5–5). They are polymorphic because their size, shape and contents change with the stage of the digestive cycle and the material digested. The forms are:

• primary lysosome: a small vesicle from the trans-Golgi network with inactive hydrolases, which are tagged with mannose-6-phosphate;
• secondary lysosome (digestive vacuole): formed when a primary lysosome fuses with a phagosome (heterophagosome), an autophagosome (autophagy of old organelles) or a secretory granule (crinophagy);
• residual body: the undigested remnants, which are expelled by exocytosis or stored as lipofuscin;
• autolysosomes (autophagosome fused with lysosome) and multivesicular bodies, which are late endosomes.

Dynamic system (diagram below): material taken in by endocytosis passes through early and late endosomes, which receive hydrolases from the Golgi and become lysosomes; autophagosomes fuse with lysosomes; the digested products leave for reuse, and the residue is expelled.

Functions: (1) intracellular digestion of proteins, nucleic acids, lipids and carbohydrates; (2) autophagy and recycling of organelles, notably during starvation; (3) defence by destroying engulfed bacteria in macrophages; (4) extracellular digestion, for example osteoclasts secreting enzymes to resorb bone, and acrosomal enzymes in fertilisation; (5) cell death, with release of enzymes in apoptosis. Lysosomal storage diseases such as Tay–Sachs and Gaucher disease result from enzyme defects.

(c) Asymmetry of glycoproteins and an overview of membrane functions

In the plasma membrane the carbohydrate chains of glycoproteins (and glycolipids) lie only on the outer (extracellular) face. This asymmetry arises in the endoplasmic reticulum and Golgi, where sugars are added in the lumen. The luminal face of the vesicle then becomes the outer surface when the vesicle fuses with the plasma membrane, and since the sugar chains are polar and bulky they cannot flip across the bilayer. The sugars form the glycocalyx, used in cell recognition (selectins, blood-group antigens), protection and immune recognition (MHC).

Membrane functions:

• Selective permeability and transport: diffusion, channels, carriers, aquaporins, and active transport such as the Na⁺–K⁺ pump.
• Signal reception and transduction: G-protein-coupled receptors, receptor tyrosine kinases and ion channels.
• Cell adhesion and junctions: cadherins, integrins, tight and gap junctions.
• Recognition, enzymatic activity and membrane potential for excitability.
• Boundary: it keeps the cell contents distinct from the environment.