🧬AP Biology Unit 4 – Cell Communication and Cell Cycle

Key Concepts

• Cell communication enables cells to respond to their environment and coordinate activities within tissues and organs
• Signaling molecules (ligands) bind to receptors on the cell surface or inside the cell triggering a response
• Signal transduction pathways amplify and transmit signals from receptors to cellular targets
• The cell cycle is a highly regulated process that controls cell division and growth
• Checkpoints at key transitions in the cell cycle ensure conditions are favorable before proceeding
• Cyclins and cyclin-dependent kinases (CDKs) are key regulators of the cell cycle
• Mitosis is the process of nuclear division that produces two genetically identical daughter cells
• Cytokinesis is the division of the cytoplasm that follows mitosis resulting in two separate daughter cells

Cell Communication Basics

• Cells communicate using chemical signals (hormones, neurotransmitters, growth factors) or direct contact
• Signaling molecules are released by signaling cells and bind to specific receptors on target cells
• Receptors can be located on the cell surface (plasma membrane) or inside the cell (cytoplasm or nucleus)
  • Cell surface receptors include G protein-coupled receptors (GPCRs), receptor tyrosine kinases (RTKs), and ion channel receptors
  • Intracellular receptors include nuclear receptors (steroid hormone receptors) and cytoplasmic receptors
• Binding of a signaling molecule to its receptor causes a conformational change initiating a cellular response
• The response depends on the type of receptor and the specific signaling pathway activated
• Cells can communicate over short distances (paracrine signaling) or long distances (endocrine signaling)
• Gap junctions allow direct communication between adjacent cells by forming channels that permit the exchange of small molecules and ions

Signaling Pathways

• Signal transduction pathways relay signals from receptors to cellular targets amplifying the signal along the way
• G protein signaling involves activation of G protein-coupled receptors (GPCRs) which activate G proteins
  • G proteins are composed of α, β, and γ subunits; activation causes the α subunit to dissociate and activate downstream effectors
  • Effectors can include adenylyl cyclase (produces cAMP) or phospholipase C (produces IP3 and DAG)
• Receptor tyrosine kinase (RTK) signaling involves dimerization and autophosphorylation of RTKs upon ligand binding
  • Phosphorylated tyrosine residues serve as docking sites for adaptor proteins which activate downstream signaling cascades (Ras/MAPK, PI3K/Akt)
• Second messengers (cAMP, Ca2+, IP3, DAG) amplify signals by activating protein kinases or opening ion channels
• Protein kinases phosphorylate target proteins modifying their activity; phosphatases remove phosphate groups
• Signaling pathways can cross-talk and integrate signals from multiple receptors to fine-tune cellular responses
• Negative feedback loops attenuate signaling to prevent excessive responses and maintain homeostasis

Cell Cycle Overview

• The cell cycle is an ordered series of events that leads to cell division and the production of two daughter cells
• The cell cycle consists of interphase (G1, S, G2 phases) and mitosis (M phase)
  • G1 phase is a period of cell growth and preparation for DNA synthesis
  • S phase is when DNA replication occurs doubling the genetic material
  • G2 phase is a period of further growth and preparation for mitosis
  • M phase includes mitosis (nuclear division) and cytokinesis (cytoplasmic division)
• Cells that are not actively dividing may enter a quiescent state called G0 where they carry out specialized functions
• The duration of the cell cycle varies among different cell types but is highly regulated to maintain proper tissue function
• Checkpoints monitor progress through the cell cycle and ensure conditions are suitable before proceeding to the next phase
  • The G1 checkpoint (restriction point) checks for growth factors, nutrients, and DNA damage before committing to cell division
  • The G2 checkpoint assesses cell size and checks for DNA damage before entering mitosis

Phases of the Cell Cycle

• Interphase encompasses G1, S, and G2 phases and is the longest part of the cell cycle
• During G1, cells increase in size, synthesize proteins and organelles, and prepare for DNA replication
  • The restriction point in late G1 is where cells commit to entering the cell cycle and dividing
  • Cells that do not receive growth factor signals or nutrients at the restriction point may enter G0 instead of proceeding
• In S phase, DNA replication occurs along with the synthesis of histones and other chromatin-associated proteins
  • DNA replication begins at multiple origins of replication and proceeds bidirectionally until the entire genome is copied
  • Cohesins are also established during S phase to hold sister chromatids together until anaphase of mitosis
• G2 phase is marked by continued cell growth, protein synthesis, and organelle production in preparation for mitosis
  • The G2 checkpoint assesses cell size and checks for DNA damage; if conditions are not met, the cell cycle is paused for repairs
• Mitosis is divided into prophase, prometaphase, metaphase, anaphase, and telophase
  • In prophase, chromatin condenses into chromosomes, and the nuclear envelope breaks down
  • Prometaphase is marked by the attachment of spindle microtubules to kinetochores on the chromosomes
  • During metaphase, chromosomes align at the cell equator (metaphase plate)
  • In anaphase, sister chromatids separate and are pulled towards opposite poles of the cell
  • Telophase sees the reformation of the nuclear envelopes around the decondensing chromosomes
• Cytokinesis overlaps with the end of mitosis and partitions the cytoplasm, organelles, and cell membrane into two daughter cells
  • In animal cells, a contractile ring of actin and myosin pinches the cell in two
  • Plant cells form a cell plate that expands to divide the cytoplasm and form a new cell wall between the daughter cells

Cell Cycle Regulation

• Progression through the cell cycle is tightly regulated by cyclins and cyclin-dependent kinases (CDKs)
  • Cyclins are regulatory subunits that bind to and activate CDKs
  • CDKs are serine/threonine kinases that phosphorylate target proteins involved in cell cycle progression
• Different cyclin-CDK complexes are active at specific points in the cell cycle
  • G1/S cyclins (cyclin D) bind to CDK4/6 and promote entry into S phase by phosphorylating the retinoblastoma protein (Rb)
  • S cyclins (cyclin A) bind to CDK2 and are required for DNA replication
  • M cyclins (cyclin B) bind to CDK1 and drive entry into mitosis
• CDK activity is regulated by phosphorylation and dephosphorylation events
  • Wee1 kinase inhibits CDKs by phosphorylating them on specific tyrosine residues
  • Cdc25 phosphatase activates CDKs by removing inhibitory phosphate groups
• Ubiquitin-mediated proteolysis of cyclins by the anaphase-promoting complex (APC) helps drive the cell cycle forward
• Checkpoints assess the status of the cell and halt the cell cycle if conditions are not met
  • The G1 checkpoint checks for growth factors, nutrients, and DNA damage; p53 plays a key role in the DNA damage response
  • The G2 checkpoint checks for cell size and DNA damage; Chk1 kinase is activated in response to DNA damage and inhibits Cdc25

Mitosis and Cytokinesis

• Mitosis is the process of nuclear division that produces two genetically identical daughter nuclei
• Prophase is marked by chromosome condensation, centrosome separation, and nuclear envelope breakdown
  • Chromosomes become visible as highly condensed structures composed of two sister chromatids joined at the centromere
  • The mitotic spindle begins to form as centrosomes move to opposite poles of the cell
• In prometaphase, spindle microtubules attach to kinetochores on the chromosomes
  • Kinetochores are protein complexes assembled on the centromeres of each sister chromatid
  • Proper attachment of microtubules to kinetochores is monitored by the spindle assembly checkpoint
• During metaphase, chromosomes align at the cell equator (metaphase plate) through the action of spindle microtubules
  • Tension generated by microtubules pulling on kinetochores helps stabilize proper attachments
• In anaphase, sister chromatids separate and are pulled towards opposite poles of the cell
  • Anaphase A involves the shortening of kinetochore microtubules, pulling chromatids towards the poles
  • Anaphase B involves the elongation of the spindle, further separating the chromatids
• Telophase is marked by the reformation of the nuclear envelopes around the decondensing chromosomes
  • The mitotic spindle disassembles, and the chromosomes begin to decondense
• Cytokinesis overlaps with the end of mitosis and partitions the cytoplasm into two daughter cells
  • In animal cells, a contractile ring of actin and myosin pinches the cell in two
  • Plant cells form a cell plate that expands to divide the cytoplasm and form a new cell wall

Connections to Other Topics

• Cell communication is essential for the proper development and function of multicellular organisms
  • Morphogens (signaling molecules) establish concentration gradients that guide pattern formation during embryogenesis
  • Notch signaling mediates lateral inhibition and controls cell fate decisions in many tissues
• Dysregulation of cell signaling pathways can lead to diseases such as cancer
  • Mutations in proto-oncogenes (Ras, Myc) or tumor suppressor genes (p53, PTEN) disrupt normal cell cycle control
  • Targeted therapies (small molecule inhibitors, monoclonal antibodies) can block specific signaling pathways in cancer cells
• The cell cycle is intimately linked to cell growth and metabolism
  • Growth factors and nutrient availability regulate entry into the cell cycle at the G1 checkpoint
  • Metabolic pathways (glycolysis, oxidative phosphorylation) provide the energy and building blocks needed for cell division
• Meiosis is a specialized cell division that produces haploid gametes for sexual reproduction
  • Meiosis involves two rounds of cell division (meiosis I and II) without an intervening S phase
  • Crossing over and independent assortment during meiosis I increase genetic variation among gametes
• Apoptosis (programmed cell death) is a highly regulated process that eliminates damaged or unwanted cells
  • Intrinsic apoptotic pathway is triggered by intracellular stress (DNA damage, ER stress) and involves mitochondria
  • Extrinsic apoptotic pathway is initiated by death receptors (Fas) in response to extracellular signals