BIOL 0500 Midterm #3

signal transduction

• the conversion of an impulse or stimulus from one physical or chemical form to another

• most often the process by which a cell responds to an extracellular signal (e.g., hormones, neurotransmitters, mitogens, etc.)

• always elicitis a specific cellular response, including changes in gene expression, protein expression, morphological changes, etc.

general principles of cell signaling

• communication between cells involves a signaling cell producing a signaling molecule that is then detected by a target cell

• target cells have both intracellular and cell-surface receptor proteins that recognize and respond to the signal molecule

• extracellular signal molecules stimulate target cells by binding to its receptor proteins

• signal transduction begins when the receptor protein on the target cell receives an incoming extracellular signal and converts it to an intracellular signal

cell signal response speed

• cells can respond to signals quickly or slowly, depending on what needs to happen inside the cell to elicit the response

• rapid cell responses are possible when the signal affects the activity of proteins already present inside the target cell (e.g., cell movement, secretion, metabolism)

• slower cell responses occur when responses require changes in gene expression and new protein synthesis (e.g., cell differentiation, increased cell growth and division)

modes of cell communication

• there are four major modes of cell communication: endocrine, paracrine, neuronal, and contact-dependent

• many of the same types of signal molecules are used for endocrine, paracrine, and neuronal signaling, the difference lying in the speed and selectivity with which signals are delivered to their targets

endocrine signaling

• endocrine communication is a slow-acting, long-lasting signaling system where endocrine glands secrete peptide or steroid hormones directly into the bloodstream (or plant sap) for distribution throughout the body

• cells that produce hormones are referred to as endocrine cells

• cortisol, estradiol, and testosterone are steroids; insulin is a protein; adrenaline and thyroxine are derivatives of the amino acid tyrosine

• examples: epinephrine (adrenal gland), cortisol (adrenal gland), estradiol (ovaries), insulin (beta cells of pancreas), testosterone (testis), testosterone (testis), thyroxine (thyroid gland)

paracrine signaling

• paracrine signaling relies on ligands released by cells into the extracellular fluid

• the ligand diffuses across the extracellular fluid to act locally, inducing changes in nearby cells (is a local mediator)

• cannot act over long distances since ligands can be restricted by degradation by enzymes, uptake by neighboring cells, or limited diffusion through the ECF

• examples: signal molecules regulating the inflammatory response, cell proliferation control, and autocrine signaling

autocrine signaling

• a type of paracrine signaling

• cells secrete factors that they themselves express receptors for to stimulate their own growth or survival

• the secreted ligand binds to the receptors on the cell’s own surface, stimulating a self-response

• cancer cells often exploit autocrine signaling

paracrine signaling examples

• epidermal growth factor (EGF) is a protein secreted by various cells to stimulate epidermal cell proliferation

• bone morphogenetic proteins (BMPs) are proteins that induce differentiation of mesenchymal stem cells into osteoblasts and cartilage

• wingless and Int-1 (WNT) is an evolutionarily conserved protein that stimulates cell proliferation (as well as embryonic development, tissue homeostasis, and cell fate)

pituitary gland

• the master regulatory gland of the body, is an endocrine gland that produces several hormones that regulate many different organs in the body

• acromegaly is a rare, slow-progressing disorder caused by excess growth hormone, leading to enlarged extremities and facial features, joint pain, a deep voice, sweating, etc.

neuronal signaling

• neuronal signals are transmitted electrically along a nerve cell axon

• once the action potential reaches the axon terminal, electrical signals are converted into chemical signals in the form of neurotransmitters, which are released into the synapse

• the neurotransmitters then diffuse across the synaptic gap to reach the membrane of the target membrane

contact-dependent signaling

• aka juxtacrine signaling

• the cell makes direct physical contact through signal molecules lodged in the plasma membrane of the signaling cell (cell-surface-bound signal molecules) and receptor proteins embedded in the plasma membrane of the target cell

• example: in embryonic development, contact-dependent signaling allows adjacent cells to become more specialized to form different cell types

• example: a transmembrane-bound Delta protein on one cell (usually prospective neurons) binds directly to Notch receptors on an adjacent cell, inhibiting neighboring cells from becoming specialized in the same way as the signaling cell

Delta-Notch signaling

• the Notch receptor itself acts as a transcription factor

• when the membrane-bound signal protein Delta binds to Notch receptors on an adjacent cell, a portion of the Notch receptor is cleaved

• the cleaved portion of Notch’s cytosolic tail migrates inwards to the cell’s nucleus

• in the nucleus, the Notch tail activates Notch-responsive genes (e.g., genes that control nerve cell production in fruit flies)

signal-receptor axis specificity

• cells within multicellular organisms are exposed to hundreds of environmental signals

• whether or not they respond to those signals depends on whether the cells possess a receptor protein for that signal

• the extracellular signal molecule alone is not the message as the message depends entirely on how the target cell receives and interprets the signal

responses elicited by acetylcholine

• demonstration of how the ligand itself doesn’t entirely convey a specific chemical message; the cell’s interpretation of the message is what constitutes the chemical message

• binding to AV node decreases heart rate

• binding to a salivary gland cell induces secretion

• binding to a skeletal muscle cell stimulates contraction

cell surface receptors vs intracellular receptors

• two broad categories of extracellular signals: (1) those that are too large or hydrophilic to cross the plasma membrane (2) those that are small enough or hydrophobic enough to diffuse across the plasma membrane

• impermeable molecules must rely on cell-surface receptors to relay their message

• permeable molecules can diffuse across the plasma membrane and bind to intracellular enzymes or receptor proteins

examples of cell-surface receptor signals

• are large, hydrophilic, or charged molecules that cannot cross the plasma membrane

• signals: growth factors (epidermal growth hormone), peptide hormones (insulin), neurotransmitters (acetylcholine)

• receptors: EGFR or ErbB1, insulin receptor (IR), nicotinic acetylcholine receptor

examples of intracellular receptor signals

• are small, hydrophobic signal molecules that can pass through the plasma membrane

• signals: steroid hormones (e.g., estrogen or cortisol)

• receptors: estrogen-cytoplasmic receptor and cortisol-cytoplasmic receptor

• upon binding cortisol, the cortisol receptor undergoes a conformational change and the activated receptor-cortisol complex moves into the nucleus, where it binds to a regulatory region and activates transcription of the target gene

combinatorial signaling

• the process whereby multiple signaling pathways interact to produce a more complex or finely-tuned cellular response

• a cell in our bodies can be exposed to several hundred positive and negative signals at a time