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Chapter 9: Cell Communication

9.1 Principles of Cell Communication Many Bacteria (pneumococcus) are able to take up DNA from environment and incorporate into own genome ability to resist antibiotic drugs o Low cell density- concentration of signaling peptide too low to stimulate DNA uptake o High cell density- concentration of signaling peptide high enough to stimulate DNA uptake

Essential elements involved in communication between all cells (prokaryotes/eukaryotes) 1. 2. 3. 4. Signaling cells Signaling molecule Receptor molecule Responding cell

Signaling cells source of signaling molecules binds receptor molecules on/in responding cell

Cell signaling: Receptor activation, signal transduction, response, termination Receptor activation: After signaling molecule binds to receptor on responding cell, the receptor is activated (turned on) Signal transduction: Once activated, receptor transmits message through cytoplasm by process calls signal transduction (often by intracellular signaling) Response: can take different forms depending on a) nature of signal b) type of responding cell Termination: allows cell to respond to new cells 9.2 Types of Cell Signaling 1. Endocrine signaling: molecules that travel through the bloodstream o Ex) estrogen, androgen 2. Paracrine signaling: two cells close together, a signaling molecule needs to diffuse only short distance to nearest neighboring cell in order to bind its receptor and deliver message (can travel distances of up to 20 cell diameters or few hundred micrometers) o Signal is usually a small, soluble molecule such as growth factor o Specialized form include communication between neurons (nerve cells), or between neurons and muscle cells 3. Autocrine signaling: signaling and responding cell are one and the same o Ex) Paracrine/Autocrine signaling especially important to multicellular organisms during development of embryo 4. Juxtacrine signaling (contact-dependent signaling): cell communication through direct physical contact, without chemical signal that diffuses/circulates through external medium o Transmembrane protein of surface of on cell acts as signaling molecule, and adjacent that of adjacent cell acts as receptor o Ex) Requires normal/healthy very targeted cell to sacrifice itself and have programmed death

Chapter 9: Cell Communication

9.3 Receptors and Receptor Activation Receptors: Proteins that receive and interpret information carried by signaling molecules Regardless of distance between communicating cells, a message is received by cells when signaling molecule binds noncovalently to its appropriate (usually highly specific) receptor protein o Signaling molecule ligand o Specific location on receptor protein ligand-binding site Binding of signaling molecule to ligand-binding site of receptor causes conformational change in receptor (activates receptor) o Through this change receptor passes message from signaling molecule to interior of cell o Similar to substrate to active site Location of particular receptor in cell depends largely on whether signaling molecule is polar or nonpolar a. Many signaling molecules (growth factors) are small, polar proteins that cannot pass through hydrophobic core of plasma membrane receptor proteins are on outside surface of responding cell o Receptor proteins are transmembrane proteins with extracellular domain, short transmembrane, and cytoplasmic domain o Entire molecule undergoes conformational change and molecule is activated when signaling molecule binds to ligand-binding site b. Nonpolar signaling molecules (steroid hormones, endocrine signaling) dont need receptors on cell surface to relay information to interior of cell o Are hydrophobic and pass easily through hydrophobic core and once inside, bind to receptor proteins located in cytosol/nucleus to form receptor-steroid complexes (can act as transcriptional regulators to control expression of specific genes) o Steroid receptors located in nucleus often already bound to DNA and need only to bind their steroid counterpart to become active o Ex) Sex hormones, glucocorticoids, ecdysone, etc. Cell-surface receptors When receptors are bound to signaling 1. G protein-coupled receptor: molecule, molecular switch is turned on, receptor couples to G proteins vice versa (proteins that bind to guanine nucleotides GTP/GDP) a. Active: bound to GTP b. Inactive: GDP 2. Receptor kinase: o Kinase- enzyme that adds phosphate group to another molecule by phosphorylation usually active/switched on o Phosphatases- remove phosphate group (dephosphorylation) inactive/switched off 3. Ligand-gated ion channel: alter flow of ions across plasma membrane when bound by ligand

Chapter 9: Cell Communication

o o o Signaling molecule binds to extracellular ligand-binding site of channel protein, channel undergoes conformational change that opens it and allows ions to flow in and out Channel remains open as long as signaling molecule remains bound Especially important for neurons/muscle cells since primary functions depend on rapid change in ion transport across plasma membrane

9.4 Signal Transduction, Response, and Termination

Chapter 9: Cell Communication

Steroid vs. non-steroid signaling Steroid signaling o Highly hydrophobic and can easily diffuse across plasma membrane o Can get into any cell but if doesnt have receptor, nothing will happen o If finds receptor, theres a conformation of complex and moves from cytosol nucleus, and can help with transcription o Processes can be relatively slow o Includes amplification (but at very different point than others), in this case at both transcription and translation results in many polypeptides

Non-Steroid signaling - Typically proteins, short polypeptides (peptides) are signals - Binds on the cell membrane - Has charged polar groups, and only signal moves across cell membrane signal transduction 1. GPLR (G-protein coupling) * focus on Wednesday Lecture 2. RTK (Receptor kinase) * 3. Ligand-gated ion channel Receptor kinase - Has hundreds of different, have different structures for ligands - Receptor tyrosine kinases have intrinsic enzymatic activity - Ligand stimulates kinase activity, often by dimerizing the receptor (the ligand doesnt have to be bivalent) - Receptor kinase phosphorylates cytosolic targets and itself (autophosphorylation) on the amino acid tyrosine - Phosphorylated tyrosines can: - - alter protein activity or location! - - be binding sites for other proteins - - be de-phosphorylated by phosphatases! - Kinase phosphorylate something