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Department of Biological and Environmental Sciences

Cell & Molecular Biology
Dr. David A. Johnson
Biol 405    4 Credits   Spring 2017  MWF 11:45-12:50 AM   PH

<<<  Cell Signaling Overview  >>>
Chapter 15

Cells use various methods of communicating with each other in the process called cell signaling. Signal molecules are released by  signaling cells and bind to a receptor on or in the target cell.
  • Direct Cell-Cell Signaling: Cell can communicate by way of direct connection between the cells. This type of direct cell to cell signaling as seen in some communication between adjacent cells during embryonic development.
  • Signaling by Secreted Molecules: Cells often communicate with other cells by secreting a molecule that travels to the target cell.
    • Endocrine Signaling: Signal molecules called hormones are released from the endocrine organ and travel through the circulatory system to the target organ. Endocrine organs include the pituitary, thyroid, parathyroids, pancreas, adrenal glands, gonads, and many others.
    • Paracrine Signaling: Some signal molecules travel to local target organs (not by way of the circulatory system). A familiar example of this type of signal molecule is the neurotransmitters that cross the synapse in nervous tissue.
    • Autocrine Signaling: Some signal molecules travel very locally, that is, the secreting cell and target cell are the same. An example is the proliferation of T cells of the immune system which is induced by antigens released by T cells.
endocrine, paracrine, autocrine signaling
  • Some Examples of Animal Signaling Molecules
    • Steroid Hormones: Steroid hormones are examples of signal molecules that can cross the cell membrane of the target cell and then bind to a receptor in the cell (they are small, hydrophobic molecules). Steroids bind to a receptor molecule in the cells that then interacts directly with the DNA to activate transcription. Steroids are made from cholesterol and include testosterone, estrogen, and progesterone (sex steroids, made chiefly by the gonads) and the corticosteroids (made chiefly by the adrenal gland). (Thyroid hormone, vitamin D, and retinoic acid are not actual steroids but function similarly.)
steroids steroids

    • NO: Nitric oxide (NO) in important in certain paracrine signaling pathways. NO is involved in the signaling that results in blood vessel dilation. In response to neurotransmitters, endothelial cells of vessels synthesize NO (nitric oxide synthetase is the enzyme that uses arginine as a substrate to form nitric oxide). NO travels to and enters nearby smooth muscle cells where it activates guanylyl cyclase which synthesizes cyclic GMP (cGMP, a second messenger molecule). This relaxes the smooth muscle, dilating the vessel. (Nitroglycerin, used in treating heart disease, is converted to NO.) NO is only a paracrine signaler because of its half-life of only a few seconds.
    • Neurotransmitters: These molecules move from a neuron to another neuron (or muscle), diffuse across the synaptic cleft and bind to receptor on the surface of the target. They include acetylcholine, dopamine, epinephrine (it also functions as a hormone secreted by the adrenal gland and is also called adrenaline), serotonin, histamine, glutamate, glycine, and GABA. (These are hydrophilic so cannot cross the membrane.) The binding opens ion channels on the target cell initiating a nerve impulse.
neurotranmitters steroids
    • Peptides: Numerous signaling molecules are peptides (a few to more than 100 amino acids) including insulin and glucagon made by the pancreas and the hormones of the pituitary gland (including growth hormone and FSH). These also cannot cross the cell membrane so bind to receptors on the cell surface.
    • Eicosanoids (like prostaglandins): These signaling molecules are lipids that bind to cell surface receptors and are paracrine signalers. They include prostaglandins, some of which which promote inflammation. One enzyme in the synthesis of prostaglandins is cyclooxygenase (COX). This enzyme is inhibited by nonsteroidal anti-inflammatory drugs (NSAIDs) like aspirin. There are 2 forms of COX: COX-1 and COX-2. Blocking COX-1 is associate with gastrointestinal problems. Aspirin inhibits both, but specific COX-2 inhibitors (for treatment of disease inflammation, Celebrex, Vioxx) have been developed, but may have other side effects (cause heart problems).
  • Mechanisms of Signaling
    • Cell Surface Receptors
      • G Protein-Coupled Receptors: This is the largest family of cell surface receptors. These are multiple-pass membrane proteins (7 times). When the signal molecule binds to the G protein-coupled receptor, the the protein undergoes a conformational change on the cytosolic side that causes G protein (on the cytosolic side) to release its GDP and exchange it for GTP. The alpha chain of G protein is therby released and can interact with adenylyl cyclase to form cAMP from ATP. cAMP (second messenger) then travels within the cell and elicits further responses. (Blood vessel growth into brains of mice and G-protein)
        • There may be as many as 1,000 types of GPCRs encoded by the human genome. Examples include receptors which bind epinephrine and prostaglandins. Also, a large percentage of the GPCRs encode olfactory receptors and GPCRs in taste cells mediate the bitter and sweet responses. Behavioral and mood regulation involves GPCRs  in the mammalian brain that bind several different neurotransmitters, including serotonin, dopamine, GABA, and glutamate.
      • Receptor Protein-Tyrosine Kinases and Cytokine Receptors and Nonreceptor Protein-Tyrosine Kinases
signal transduction signal transduction
  • Intracellular Signal Transduction: cAMP and Others
    • As seen above, signal molecules like hormones may cause an increase in intracellular cAMP (second messenger) concentration by activating adenylyl cyclase. cAMP may then activate protein kinase A (C in the figure).
    • Protein kinase phosphorylates proteins, in some cases activating them and in other cases inactivating them.

Case Study: Angiotensin, angiotensin-converting enzyme (ACE), angiotensin receptors (AT1, AT2), and ACE inhibitors:
AT1 and AT2 are G protein-coupled receptors.

  • What is angiotensin?
  • What does it bind to?
  • What are the sequence of events resulting from its binding and the overall consequence?
  • What specifically do ACE inhibitors do and what is their overall effect?
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