1 00:00:08,880 --> 00:00:24,370 A biological individual consists of multiple organs with specialized functions. 2 00:00:24,829 --> 00:00:29,929 For the organism to function properly in its environment, these organs must communicate. 3 00:00:30,629 --> 00:00:34,689 This communication often involves a signal sent from one location to another 4 00:00:34,689 --> 00:00:38,810 that instructs the second organ about the status of some cellular feature. 5 00:00:39,530 --> 00:00:41,009 Glucose is a good example. 6 00:00:41,909 --> 00:00:44,270 Glucose is a critical product of digestion. 7 00:00:45,369 --> 00:00:48,270 It is an essential energy source for cellular metabolism. 8 00:00:49,130 --> 00:00:56,350 This energy is produced when glucose is used as a substrate for glycolysis and then the Krebs or citric acid cycle. 9 00:00:57,210 --> 00:01:04,810 Following the digestion of food, higher levels of glucose circulate through the bloodstream, where it enters different cell types. 10 00:01:04,810 --> 00:01:12,409 In muscle cells, glucose is readily used to produce energy and is also stored as glycogen, 11 00:01:12,969 --> 00:01:15,469 a secondary short-term energy source. 12 00:01:18,120 --> 00:01:24,519 In fat cells, glucose is used for triglyceride production and acts as an important energy reserve molecule. 13 00:01:25,659 --> 00:01:31,060 Here, we will illustrate the signaling pathway that occurs when glucose is at high levels. 14 00:01:31,680 --> 00:01:35,219 This pathway involves multiple proteins and signaling events. 15 00:01:35,219 --> 00:01:37,920 This is termed cytoplasmic signaling. 16 00:01:38,799 --> 00:01:44,019 Different types of cells perform similar signaling steps in response to changes in their environment. 17 00:01:45,180 --> 00:01:50,900 In the protein recycling animation, we see a group of storage vesicles enriched with GLUT4 proteins 18 00:01:50,900 --> 00:01:56,219 continuously recycling from the cell membrane to an inactive location in the cytosol. 19 00:01:56,719 --> 00:02:00,879 GLUT4 is a protein that facilitates the movement of glucose into the cell. 20 00:02:00,879 --> 00:02:07,879 When high levels of glucose are detected by beta cells in the pancreas, insulin is released by the cells. 21 00:02:07,879 --> 00:02:16,879 The insulin circulates through the bloodstream until it binds to an insulin receptor embedded in the cell membrane of a muscle, fat, or brain cell. 22 00:02:16,879 --> 00:02:23,879 Once the insulin binds to the receptor, phosphate groups are added to the intracellular domain of the receptor. 23 00:02:23,879 --> 00:02:29,879 Since the receptor itself adds the phosphate groups, the process is called autophosphorylation. 24 00:02:29,879 --> 00:02:36,219 Phosphorylation. This phosphorylation event sets off a cascade of molecular events. 25 00:02:37,159 --> 00:02:42,319 The activated receptor protein then adds a phosphate group to another closely associated 26 00:02:42,319 --> 00:02:48,099 protein. This effectively passes the signal from the receptor to the next step in the signal 27 00:02:48,099 --> 00:02:55,439 pathway. Proteins that add phosphate groups to another protein are called kinases. Kinases are 28 00:02:55,439 --> 00:03:01,360 often components of signal pathways, and phosphorylation is an important component in the transmission 29 00:03:01,360 --> 00:03:06,860 of a signal from one compartment to another. In this system, the signal corresponds to 30 00:03:06,860 --> 00:03:13,599 the level of blood glucose and is transmitted from outside to inside the cell. Next, we 31 00:03:13,599 --> 00:03:18,659 see a large pool of molecules that are embedded in the membrane also being phosphorylated. 32 00:03:19,740 --> 00:03:25,060 Other proteins are then in turn phosphorylated, further transmitting the first extracellular 33 00:03:25,060 --> 00:03:28,240 signal that was originally sent from outside the cell membrane. 34 00:03:29,379 --> 00:03:31,659 So how does this affect the uptake of glucose? 35 00:03:32,599 --> 00:03:38,840 As we mentioned before, GLUT4 is a glucose transporter, and GLUT4 storage vesicles are 36 00:03:38,840 --> 00:03:41,159 held in a recycling state near the cell membrane. 37 00:03:41,919 --> 00:03:47,020 The vesicles are held mostly in this region because the RAB proteins that interact with 38 00:03:47,020 --> 00:03:52,060 the motor proteins necessary to move the vesicles to the membrane are in an inactive state. 39 00:03:52,060 --> 00:03:58,960 A final step in this signal pathway involves the phosphorylation of a protein that prevents 40 00:03:58,960 --> 00:04:03,379 the RAB proteins from interacting with the vesicles. 41 00:04:03,379 --> 00:04:08,259 When the RAB proteins are no longer inhibited, the storage vesicles can freely merge with 42 00:04:08,259 --> 00:04:10,900 the membrane. 43 00:04:10,900 --> 00:04:16,060 Once the vesicles have merged, many GLUT4 proteins are embedded in the membrane and 44 00:04:16,060 --> 00:04:20,680 large quantities of glucose can move into the cell. 45 00:04:20,680 --> 00:04:25,759 It is the signaling pathway that ensures only the correct molecules will be allowed to enter 46 00:04:25,759 --> 00:04:26,740 the target cell.