Biology Chapter: Cell Communication and Diabetes

Cell Communication

• Cells are the fundamental units of life, working together in multicellular organisms like humans.
• Cell functions & body functions rely heavily on cellular communication.
• Tissues: groups of cells with shared functions. Example: beta cells in pancreas produce insulin.
• Organs: structures formed by multiple tissues, performing specific tasks.
• Organ systems: groups of organs, working together for particular functions (e.g., circulatory, endocrine, digestive).
• Cells communicate through chemical signals.
• Two major chemical signals: lipids (nonpolar, can cross membranes) and proteins (polar, water-soluble).
• Lipid-based signals (e.g., steroid hormones like testosterone) and protein hormones derived from amino acids, polypeptides can pass right through the membrane (epinephrine).

How Cells Communicate

• Direct cell-to-cell communication:
• In plants, plasmodesmata (channels connecting plant cell cytoplasms) facilitate direct transfer of molecules between cells.
• In animals, gap junctions (channels linking animal cell cytoplasms) allow direct molecules transfer. Also, tight junctions (hold cells together) form barriers in tissues (e.g., intestines).
• Immune system communication: Helper T cell recognizes antigens (part of pathogen), activates, releases cytokines (messages) which help other immune cells fight infection. Cytotoxic T cells damage infected cells by creating holes.
• Local regulators: short-distance communication through chemical signals. Example: mast cells release histamine (inflammatory substance), causing localized inflammation (redness, swelling, heat). Chemokines attract phagocytic cells.
• Neurotransmitters: chemical signals in nerve cells; released from presynaptic cell; travel across synapse to postsynaptic cell; calcium ions are vital.

How cells communicate over long distances

• Hormones: chemical signals that travel within the bloodstream for long-distance communication. The endocrine system utilizes hormones to regulate many body functions. Released from glands to bloodstream, needing receptor proteins in target cells.

### Signal Transduction

• Signal transduction pathways: linking signal reception to cellular responses.
• Ligand: chemical message; binds with a receptor. Example: epinephrine.
• Signal reception: ligand attaches to a receptor protein.
• Intracellular receptors: located inside the cell; for lipid-based hormones (e.g., steroids).
• Extracellular receptors: located on the cell surface. For protein-based hormones (e.g., epinephrine).
• 3 types of surface receptors:
• G protein-coupled receptors: (using epinephrine as an example)
• Ligand binding changes the receptor shape which activates a G protein.
• The activated G protein subunits initiate a signal transduction cascade:
• The receptor changes shape → activates a g protein → g protein has an activated alpha subunit which separates from the rest of the protein, → activate adenylyl cyclase → adenyl cyclase converts ATP to cAMP → cAMP activates protein kinase A (PKA).
• PKA activates other enzymes, creating a phosphorylation cascade, amplifying the signal.
• cAMP is a second messenger.
• The phosphorylations and dephosphorylation cascades that occur with the different proteins cause the signal to increase (amplify)
• The original ligand causes a metabolic response, ex: raised blood sugar levels.
• Receptor tyrosine kinases:
• Signaling starts when ligand binds to the receptor tyrosine kinase (RTK) and activates the receptor.
• The activated receptors cause themselves to "auto-phosphorylate" (add phosphate groups to themselves).
• Relay proteins bind to the phosphorylated tyrosines, initiating a cascade of further signals to the cell.
• Ligand-gated ion channels:
• When a signaling molecule (ligand) binds to the ligand-gated ion channel, it causes the gate to open, allowing ions to flow in and out of the cell, and initiating a cell response.
• Binding of a ligand opens the gate; ions flow across the membrane causing a response.

Signal Transduction Pathways- Examples

• Glucose regulation:
• Insulin binds to its receptor, which initiates intracellular signaling pathways. Signaling starts with insulin.
• These pathways result in the activation of enzymes related to lipid metabolism & glycogen synthesis.
• GLUT4 protein activation (a carrier for glucose): GLUT4 transport vesicles embed in the cell membrane, increasing glucose uptake.
• Ethylene signaling (plants):
• A gaseous plant hormone that triggers fruit ripening in a positive feedback loop, activates genes that result in a positive feedback loop. The activation of downstream target proteins activate more genes, which causes the ripening to speed up.

Changes in Signaling Pathways

• Mutations in signaling pathway components can disrupt the transduction of signals. This can lead to aberrant cellular responses like those seen in cancer.
• Changes in extracellular or intracellular domains of receptors can block signal transduction.
• Mutations in relay proteins can lead to uncontrolled cell division, a hallmark of cancer.

Feedback Mechanisms

• Feedback mechanisms: regulate cellular processes, maintaining homeostasis.

• Negative feedback loops: maintain a steady-state within the body or cells. Often involve hormones, regulate blood sugar levels.

• Example (blood sugar regulation):

• High blood sugar → promotes insulin release → lowers blood sugar. Receptor proteins detect high blood sugar in the bloodstream, & release insulin → target cells take up the glucose until blood sugar decreases.

• Positive feedback loops: amplify a response. 

• Examples (childbirth, blood clotting):

• Childbirth: contractions cause further contractions.

• Blood clotting: initiated clotting produces more clotting.

Cell Cycle

• The cell cycle: series of events that result in cell division.
• Interphase: G1, S, G2 phases.
• M phase (mitosis): division of nucleus, produces two identical daughter cells.
• The nucleus is dividing.
• Phases: prophase, metaphase, anaphase, telophase.
• Control points (checkpoints): crucial for the cell to move from one stage to the next. Checkpoints ensures DNA replication is complete, chromosomes are correctly aligned, and no damage.
• G1 checkpoint: checks cell size, nutrients, growth factors, and DNA integrity before DNA replication begins.
• G2 checkpoint: checks the integrity of the DNA after replication, and prepares for M phase.
• M checkpoint: checks if chromosomes are properly attached to spindle fibers (microtubules) before the cell divides.
• Cyclins/CDK: proteins that control the progression of the cell cycle.
• Genes regulating cell division: Normal genes (proto-oncogenes); mutated can be oncogenes, leading to cancer; also tumor suppressor genes limit cell division.
• P53: a tumor suppressor gene, regulates cell cycle checkpoints; vital for DNA damage repair and initiating apoptosis.

Feedback loops and Diabetes

• Diabetes: imbalance of blood glucose regulation.
• Type 1: autoimmune disease; body doesn't produce insulin.
• Type 2: insulin resistance; cells don't respond properly to insulin.
• Mechanisms for maintaining homeostasis; Negative feedback loops maintain homeostasis, so when one component increases, it activates a cascade of other factors to decrease it.
• Hypothalamus: Monitors blood osmolarity, regulating ADH release from the posterior pituitary. Negative feedback loop.
• Insulin resistance/Type 2: Impaired insulin signaling pathways, preventing glucose uptake even if insulin is bound to its receptor.