UNIT 4 AP Bio: Cell Communication & Cell Cycle

Cell communication is crucial for maintaining homeostasis and coordinating cellular activities. This process can occur through various mechanisms, including:

• Direct Contact: Cells can communicate through gap junctions or plasmodesma, allowing for the direct transfer of molecules.

• Local Signaling: Involves the release of signaling molecules that affect nearby cells, such as neurotransmitters in synaptic signaling.

• Long-Distance Signaling: Hormones are released into the bloodstream, affecting target cells at distant locations in the body.

Steps of Signal Transduction Pathway

• Reception-detection of signal

• transduction- convert signal

• response - specific cellular response

• Common Cell Receptors

  • G-protein-coupled receptors (GPCRs) are embedded in the cell membrane, with one end exposed to the extracellular environment and the other inside the cell. They are also involved in many physiological processes and are important drug targets for various diseases.

  • GPCRs detect molecules outside the cell like hormones, neurotransmitters, or sensory stimuli (light or odors). Each GPCR is specific to certain ligands

  • Activation: G-proteins have 3 subunits: alpha, beta, and gamma.

    • in an inactive state, the alpha subunit is bound to GDP

    • GCPR activates G-protein, the GDP replaces GTP (stronger energy source) and the alpha subunit separates from the beta-gamma.

  • The separated alpha subunit and beta-gamma interact with other proteins or enzymes in the cell, triggering various signaling pathways

    • these pathways can lead to changes in cell activity, gene expression, or ion channel function

    • Functions of GCPR:

      • sensory perception: vision, taste, smell

      • hormonal regulation

      • neurotransmission

      • immune system function

    • overall, GPCRs act rapidly and control short-term responses

  • Ion Channel Receptor also called ligand gated ion channel receptors

    • specialized proteins in the cell membrane that allow ions to flow in and out of the cell in response to specific signals.

    • How do they work?

      • a specific ligand such as a neurotransmitter binds to receptors extracellular domain

      • receptor changes shape, allowing for ion channel to open. Ions such as Na, K, Ca, Cl move through it along their electrochemical gradient (from areas of high concentration to low concentration)

      • they respond to external stimuli (like ligands binding) by opening and closing, allowing the ions to pass through the membrane

      • Response: the ions change the cell’s electrical charge and activates cellular responses.

        • example: in neurons, this can trigger or inhibit an action potential or in muscle cells it can lead to contraction.

      • overall, ion channel receptors directly allow ion flow

  • Receptor Tyrosine Kinase (RTK) : membrane receptors that play a vital role in cell growth, differentiation, metabolism, and survival.

    • they act as molecular switches that translate extracellular signals into intercellular actions by activating signaling pathways.

    • RTKs are transmembrane proteins with 3 main regions

      • Extracellular Domain: binds to ligands such as; growth factors, cytokines, or hormones

      • Transmembrane Domain: secure the receptor in the cell membrane

      • Intracellular Domain: contains a tyrosine kinase enzyme that can transfer phosphate groups to specific residues on proteins

    • Dimerization: ligand binding causes two RTK molecules to come together, forming a dimer. A critical step to activation!

      • Autophosphorylation: tyrosine kinase in the RTKs becomes active. The receptors add phosphate groups from ATP to other proteins.

      • this also indicates multiple intercellular signaling pathways, which regulate cellular responses.

    • Cell Responses: RTK activation can lead to..

      • cell division

      • cell growth

      • Survival or apoptosis(programmed cell death)

    • Overall, RTKs are slower because they focus on long term processes like growth.

• Phosphorylation Cascade (PCs): a series of chemical reactions where one enzyme activates another by adding a phosphate group to it, which sets off a chain of reactions that amplifies and transmits a signal within a cell.

  • PCs must be tightly regulated, if they become overactive or inactive they can lead to diseases such as:

    • Cancer

    • Diabetes

    • Neurodegeneration

Different Types of Cell Signaling

• Autocrine: a cell produces a signal and acts on itself or on cells of the same type.

  • Often used for self-regulation or amplification of a signal

• Paracrine: the signal is sent to neighboring cells within a short distance. The signal diffuse locally through the extracellular space

  • synaptic signaling in neurons

  • wound healing

• Endocrine: signal travels a long distance through the bloodstream to reach target cells

  • Pituitary gland releases a hormone which affects all cells in the body

  • insulin, released by pancreas, regulates glucose uptake in tissues

• Juxtacrine: cells communicate trough direct physical contact. This needs the ligand to be bound to the signaling cell or be a part of its surface

  • immune system

  • development

• Gap Junction: small molecules or ions to pass directly between adjacent cells without for extracellular signaling molecules

• 2nd Messenger’s Breakdown

  • Small intercellular molecule that relay signals from receptors on the cell surface to target molecules within the cell.

  • they play a crucial role in amplifying the signal and triggering a specific cell response

  • 2nd messenger examples: cAMP, IP3, adenylyl cascade

    • cAMP: comes from ATP and activates protein kinase

      • examples: Glycogen Breakdown, Heart Rate, Hormone secretion

    • IP3: derived from the cell phospholipid in the cell membrane, DAG is also formed in the process

      • DAG remains in the membrane and activates protein kinases

        • example of IP3/DAG: muscle contraction, secretion, immune response

    • Adenylyl Cascade: revolves around the production of cAMP by the enzyme adenylyl cyclase. It is a prominent pathway in GCPR signaling

      • Amplifies cell signaling

        • examples: fight or flight responses, metabolic regulation, ion channel regulation

      • inhibition of adenylyl cyclase results in reduced cAMP levels

Cell Cycle

• DNA is organized into discrete units called chromosomes

  • each chromosome contains one long DNA molecule associated with many proteins

• Phases of Cell Cycle

  • Interphase

    • G1 Phase (Gap 1):

      • cell grows and performs normal functions

      • prepares for DNA replication

        • DNA is dispersed in the nucleus as long strands of chromatin

          • Checkpoint ensures the cell is ready for DNA synthesis

    • S Phase (Synthesis):

      • DNA is replicated

      • each chromosome duplicates to form two sister chromatids held together by a centromere

    • G2 Phase (Gap 2):

      • cell grows further and prepares for mitosis

      • proteins and organelles are synthesized

        • checkpoint ensures DNA replication is complete and error-free

    • Mitotic Phase (M phase):

      • Division of the nucleus and cytoplasm

        • 2 main process

          • Mitosis: division of genetic material

          • Cytokinesis: division of cytoplasm

• Mitosis: Steps of Nuclear Division

  • Prophase:

    • chromatin condenses into visible chromosomes

    • mitotic spindle begins to form (spindle apparatus)

    • nuclear envelope starts to break down

  • Prometaphase:

    • nuclear envelope fragments

    • Microtubules attach to kinetochores on chromosomes

  • Metaphase:

    • chromosomes align at the metaphase plate

    • spindle checkpoint ensures all kinetochores are attached to microtubules

  • Anaphase:

    • sister chromatids separate and move to opposite poles

    • Shortening of the spindle microtubules

  • Telophase:

    • nuclear envelopes reform around two sets of chromosomes

    • chromosomes de-condense back into chromatin

    • two distinct daughter nuclei form in the cell

  • Cytokinesis: the separation of the cytoplasm

    • in animal cells: formation of cleavage furrow

    • in plant cells: formation of cell plate

• Regulation of Cell Cycle

  • Checkpoints

    • G1 checkpoint-determines if cell proceeds to S phase

    • G2 checkpoint-ensures DNA replication is complete and damage free

    • M checkpoint- ensures chromosomes are properly aligned at metaphase plate

  • Cyclins and Cyclin-Dependent Kinases (CDKs)

    • Cyclins: regulatory proteins that fluctuate in concentration during the cycle

    • CDKs: enzymes activated by cyclins to drive cycle progression

      • Example: Cyclin-CDK complexes—> aka MPF (Maturation Promoting Factor)

  • Internal and External signals

    • these help regulate the cell cycle and promote cell growth

      • Internal: signals from within the cell that monitor DNA. If DNA is damaged, then replication is incomplete

      • External: signals from outside the cell such as growth factors, density-dependent inhibition (crowded cells stop dividing), anchorage dependent (cells attached to a substrate to divide

  • Cancer Cells

    • cancer results from uncontrolled cell division due to the malfunctioning cell cycle regulation

    • Key Factors:

      • mutations in proto-oncogenes (become oncogenes)

      • loss of function in tumor suppressor genes

    • cancer cells bypass normal checkpoints, leading to tumor formation

    • the spread of cancer cells is called metastasis

      • cells of the benign tumors do not metastasize; those of malignant tumors do

• Key Terms and Concepts

  • Chromatin: Condensed DNA

  • Chromosome: Condensed DNA

  • Sister Chromatids: Identical copies of a chromosome

  • Centromere: region holding sister chromatids together

  • mitotic spindle: structure of microtubules controlling chromosome movement

  • kinetochores: protein structures in chromatids where spindle fibers attach

  • apoptosis: programmed cell death, essential for development and maintenance