Hello everyone, welcome to my Coursera class, basic principles of cell signaling. This is Session 3, Week 5. Today we're going to study about other membrane receptor pathways. The study objective for this session is to understand the basic concepts of diverse membrane receptors. We have so far studied major membrane receptor signaling pathways. First one was membrane receptor tyrosine kinase in insulin and EGF receptor signaling pathway. Secondly, we have studied serine/ threonine kinases, and next, G protein coupled receptor signaling pathways have been reviewed. More than that, we have studied tyrosine kinase-associated receptor, particularly in the cytokine and associated signaling pathways. We have studied the JAK/STAT signaling pathway. Previously, we also studied cell-cell adhesion receptor pathways such as Notch signaling pathway. Other than those major signaling pathways, there are many various and diverse membrane receptors and related signaling pathways. I'm going to introduce more interesting unique types of membrane receptors. Membrane receptor tyrosine phosphatase. This enzyme and membrane receptor can remove specific phosphate groups from phosphorylated tyrosine residues on proteins. The point is, this membrane signaling receptor is protein tyrosine phosphatase, thus the activation of this membrane receptor tyrosine phosphatase can suppress receptor tyrosine kinase signaling pathway. Ligands include growth factors, cytokines, and so on. Next one I want to introduce is receptor guanylyl cyclase. As its name indicates, this membrane receptor has unique guanylyl cyclase activity. Guanylyl cyclase can catalyze the synthesis of cyclic GMP from GTP. Let me show a great example about receptor guanylyl cyclase. The most popular and famous one is atrial natriuretic peptide, ANP, signaling pathway. ANP is synthesized and secreted by cardiac muscle cells in the atria of the heart. The main function of this hormone is to regulate blood pressure. Thus the ANP hormone can promote the excretion of water and sodium in the kidney. Activation of ANP receptor, which is guanylyl cyclase, can promote the synthesis of cyclic GMP. Throughout this receptor guanylyl cyclase action, the increased cyclic GMP can activate a cyclic GMP-dependent protein kinase called PKG. Subsequently, activated PKG can phosphorylate many other important signaling proteins to further mediate ANP actions in the control of blood pressure. The figure on your right summarizes the action of ANP receptor. Again, the activation of ANP receptor can catalyze the synthesis of cyclic GMP, and this second messenger cyclic GMP trigger subsequent signaling cascades. The next interesting receptor is integrin receptor. Cells can sense extracellular matrix called ECM, such as fibronectin and collagen. They are present in the outside of the cell as a form of extracellular matrix. This cell, ECM signaling is very critical for controlling cell proliferation, migration, and even cellular death. Integrin is a membrane receptor. When bound to specific extracellular matrix, integrin receptor molecules can be clustered, and become activated. Activated integrin receptor can transmit intracellular signaling cascade through protein tyrosine kinases, such as a focal adhesion kinase called the FAK, F-A-K. As you see the cell stained images on your left, the red dots indicate the point of ECM cell interaction, which are integrin receptor related. You're looking at the summary slide on your right, the interaction between extracellular matrix and its receptor integrin, and the cellular membrane can trigger the signaling cascade in the downstream throughout protein phosphorylation, protein-protein interaction, as well as signaling second messengers. Next, I would like to introduce ligand-gated ion channel. We have studied voltage-gated ion channel during electrical signaling session. These type of ion channel is very unique in that it can be activated upon specific chemical-ligand interaction. Thus, opening and closure of this ion channel can be tightly regulated by specific ligands. As the figure clearly summarizes, upon the interaction between the channel and the ligands, the channel status, I mean the opening and closure of the pore can be controlled. Great example can be found from channel proteins in the synapse. For example, when the neurotransmitter glutamate in the synapses rises, the glutamate-bound NMDA channel, can increase its channel activities. When glutamate-bound NMDA channel is activated, channel opening is increased, and calcium and sodium ions can be fluxed into the post-synapse thus the membrane can be depolarized. Second example is GABA. GABA s gamma-aminobutyric acid, which is inhibitory neurotransmitter. When GABA neurotransmitter binds to its binding target channel, GABA channel, then GABA channel is activated, then in this case, chloride ions can be transported into the post-synapse. Thus, neuronal membrane can be hyperpolarized. By showing this summary, I'm going to include electrical and chemical signaling altogether in the area of synapse. First, action potential can reach axon terminal and depolarize the membrane. Voltage dependent calcium channel can be opened, and calcium ions coming in. Subsequently, calcium signaling second messenger can trigger a synaptic or a vesicle fusion events, thus release neurotransmitters. The neurotransmitters can bind to their specific receptors, then thus activate specific ion transport into the post-synapse, thus control the membrane depolarization status. As I previously introduced, some neurotransmitters, they can trigger specific membrane potential changes through ligand-gated ion channels. As you see the figure in the bottom, the interaction between the neurotransmitter and ligand-gated ion channels can facilitate the transport of ions into the post-synaptic area. Thank you very much for your attention.