SC430 Molecular Cell Biology Welcome to Unit 7 Seminar with Dr Hall-Pogar Tonight we will discuss –Diseases that result from errors in cell signaling pathways and available treatments –I will be available at AIM:KaplanHallPogar before and throughout the seminar if you have any questions or issues. We will begin promptly at 8:00pmET

2 Unit Review DB Project –Cover Letter

3 Cell to Cell Communication Juxtacrine signaling - with each other via direct contactJuxtacrine signaling Paracrine signaling - over short distancesParacrine signaling Endocrine signaling - over large distancesEndocrine signaling Some cell-to-cell communication requires direct cell-cell contact cells form gap junctionscell-cell contactgap junctions

4 Cell signaling: responding to the outside world Cells interact with their environment by interpreting extracellular signals via proteins that span their plasma membrane called receptors Receptors are comprised of extracellular and intracellular domains The extracellular domain relays information about the outside world to the intracellular domain The intracellular domain then interacts with other intracellular signaling proteins These intracellular signaling proteins further relay the message to one or more effector proteins Effector proteins mediate the appropriate response

5 Receiving the Signal: G-protein Coupled Receptors (GPCRs) GPCRs are an important and ubiquitous class of eukaryotic receptors (>700 in humans) The intracellular domain is coupled to a heterotrimeric G- protein When the G  subunit is bound to GDP it is “OFF”; when it is bound to GTP it is “ON” When the extracellular domain binds to the signal molecule, it causes a conformational change relayed through the transmembrane spans to the intracellular domain The conformational change relayed to the intracellular domain causes the G  subunit to release GDP and bind to GTP thereby activating both the G  and G  /G  subunits

6 What are G-proteins? G proteins bind GTP: guanosine triphosphate. Control and amplify intracellular signaling pathways Exist in two states 1) bound GTP: active 2) bound GDP: inactive Fig Examples of GTPase proteins Ras, Cdc-42 (hormone, GF, drug)

7 GTPases and disease. Rho GTPases are involved in the regulation of critical cellular process such as cell proliferation, attachment, migration, gene expression and apoptosis. Damage to these small GTPase switches can have catastrophic consequences for the cell and the organism. Several small GTPases of the Rac/Rho subfamily are direct targets for clostridial cytotoxins. Ras proteins are mutated to a constitutively-active (GTP-bound) form in approximately 20% of human cancers.

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9 The Study of Smell Yau, Ph.D., professor of neuroscience in Johns Hopkins' Institute for Basic Biomedical Sciences –"In the nose, an odor molecule that's inhaled probably stays in the nasal mucus long enough to bind to and trigger a number of receptors, essentially enhancing its own signal.” –"The sense of smell needs to be sensitive, but amplification isn't the only way to improve sensitivity.” The cells could have many copies of the receptor, or many cells could express the same receptor. These are most likely the reasons why mice and dogs have a heightened sense of smell compared to people

10 Night Vision Rhodopsin is the light-absorbing pigment of the rods. This G-protein-coupled receptor (GPCR) is incorporated in the membranes of disks that are neatly stacked in the outer portion of the rod. Retinal –Undergoes a physical change that triggers a chain of events culminating in a change in the pattern of impulses sent back along the optic nerve. –Ultimately, the reduction in glutamate release activates some interneuron pathways, inhibits others. The interplay of excited and inhibited interneurons modulates the spontaneous firing of the ganglion cells to which they are connected and gives rise to the ability of the retina to discriminate shapes.