Cell Communication and Signaling

• Cell signaling is essential for multicellular organisms to coordinate development, adapt to their environment, and maintain function.
• Cells use ligands (signaling molecules) and receptors (target cell regions) for communication. Receptors are made of proteins.
• Ligands bind to receptors on target cells.
• Message relayed by the ligand through chemical messengers inside of the cell, is called signal transduction pathway
• Cellular responses include healing, immune activation, and changes in gene expression.
• Different cells have different collections of proteins, resulting in varying signal detection and response.

How Cells Communicate

• Cells communicate using direct contact via intercellular pores called plasmodesmata (plants) and gap junctions (animals).
• Macrophages display broken-down antigen parts on membrane proteins, activating helper T cells to signal B cells.
• Local signaling involves cells sending ligands over short distances, including paracrine and synaptic signaling.
• Long-distance signaling (endocrine) uses hormones secreted into the bloodstream to reach distant target cells, regulating growth, development, metabolism, and behavior.

Transduction Pathway Features

• Internal receptors inside the cell modify protein synthesis (e.g., thyroid and steroid hormones).
• Ligand-gated ion channels open in response to ligand binding, altering ion flow and producing a response.
• GPCRs (G protein-coupled receptors) respond to extracellular signals (hormones, neurotransmitters) and trigger intracellular signaling cascades.
• Inactive G proteins have GDP (guanosine diphosphate) bound; activation swaps GDP for GTP (guanosine triphosphate).
• Activated G protein subunits interact with other proteins to initiate a signaling pathway.

Second Messengers

• The ligand binding to the receptor acts as a pathway's "first messenger."
• Second messengers are small, nonprotein molecules or ions that spread throughout a cell by diffusion.
• Common second messengers include cyclic AMP and calcium ions.

Protein Kinase and Phosphorylation

• Protein kinases activate other proteins via phosphorylation (adding a phosphate group from ATP).

Termination of Signal

• Inactivation mechanisms are essential for cell signaling.
• Receptors return to their inactive state when signal molecules leave.
• Ligands are either broken down or reabsorbed after use.
• Multistep pathways amplify signals and provide more opportunities for coordination and regulation.
• Few molecules can produce a large cellular response through signal amplification in multistep pathways.

Homeostasis and Feedback Loops

• Homeostasis is the ability to maintain a stable internal environment.
• Failure of homeostasis can lead to disease or death.
• Feedback loops help maintain equilibrium: positive (amplifies) or negative (inhibits) effects on the system.
• Negative feedback loops maintain variables at a set point (e.g., thermostat regulating temperature).
• Positive feedback loops amplify changes, moving the system away from equilibrium (e.g., fruit ripening.)
• Positive feedback loops are less common than negative feedback loops.

Cell Life Cycle

• Cells divide to replace worn-out or damaged cells, to facilitate growth, and to reproduce.
• Uncontrolled cell division results from mutations (cancer).

Interphase

• Cells spend most of their life in interphase, doing their jobs and preparing for cell division.
• G1 stage: Growth occurs, and proteins for division are made. Cell division can be triggered by available space nearby the cells. Chemical signals mediate cell spacing.
• S stage: DNA is copied, resulting in two sets of DNA
• G2 stage: Cells continue to grow with an increase in organelles, and synthesize proteins (e.g., spindle fibers) for division.
• G0 stage: Cells not actively dividing (e.g., some muscle and nerve cells) enter G0. They will not leave G0 unless another cell signals for them to divide.

Mitosis

• Mitosis divides the DNA into two nuclei, each with a complete set.
• Prophase: Chromatin condenses into chromosomes, the nuclear envelope breaks down, and centrioles move to opposite poles. Kinetochores develop for microtubule attachment.
• Metaphase: Chromosomes line up on the metaphase plate via spindle fibers, ensuring sister chromatid separation.
• Anaphase: Spindle fibers pull sister chromatids apart to opposite poles of the cell.
• Telophase: Two new nuclei form, chromosomes uncoil into chromatin, and the cell membrane begins to pinch.
• Cytokinesis: The cell membrane finishes dividing, resulting in two daughter cells, each with their own DNA. They start their own life cycle.
• Plant cells build a cell plate during telophase, becoming part of the cell wall for both daughter cells.

Cell Cycle Checkpoints

• Growth factors (signaling proteins/ligands) signal a cell to divide.
• Checkpoints regulate cell division, stopping or proceeding based on conditions.

G1 Checkpoint

• It is the primary checkpoint, deciding to divide, delay, or enter G0.
• DNA damage can halt division and is regulated by the signaling protein p53 .
• P53 triggers DNA repair enzymes or inhibitors to pause cell division.
• High p53 levels can trigger apoptosis (programmed cell death), losing contact with its neighbors, and causing cells to collapse, later consumed by white blood cells.
• Apoptosis is vital in organism development (e.g., tadpole tail loss, removal of webbing in human digits).

G2 Checkpoint

• Assesses DNA replication success after the S stage.
• DNA repair can be initiated by p53.
• Mitosis begins if this checkpoint passes.

M Checkpoint

• Stops cell division during metaphase if spindle fibers aren't properly attached to chromosomes.

Checkpoint Regulation

• Cyclins change in concentration during the cell cycle; specific cyclins must be present for the cycle to continue.
• Cyclins partner with cyclin-dependent kinases (Cdk), activating Cdks as kinases.
• The Cyclin-Cdk complex activates specific target proteins for the next cell cycle steps.
• When cyclin is degraded, Cyclin-Cdk complexes can no longer be made, which deactivates Cdks.

Cancer

• Cancer results from mutated genes that regulate the cell cycle.
• A tumor is an abnormal tissue growth.
• Metastasis is the spread of tumors from their origin to other areas of the body.
• Angiogenesis allows cancer cells to direct new blood vessel growth for increased nutrients and oxygen, supporting growth and spread.
• Cancer originates from imbalances between signals that promote and inhibit cell division.
• Proto-oncogenes code for proteins (cyclins) that promote the cell cycle; mutations create oncogenes that cause cancer.
• Tumor suppressor genes code for proteins (p53) that inhibit the cell cycle and promote apoptosis; mutations can accelerate the cell cycle uncontrollably.