Intercellular communication

Transcription

1 Intercellular communication Dewajani Purnomosari Department of Histology and Cell Biology Faculty of Medicine Universitas Gadjah Mada

2 Outline General principle of intercellular communicabon Signal molecules and their receptors Hydrophobic molecule vs intracellular receptor Hydrophilic molecule vs trans membrane receptor Signal transducbon and cellular response 2

3 Why the cell need to communicate? To make mulbcellular organism 3

4 Why the cell need to communicate? The signals determine cell s faith To perform special task Homeostasis AdaptaBon and survival 4 Figure 15-8 Molecular Biology of the Cell ( Garland Science 2008)

5 How s the cell communicate to each other? The way cells communicate is determined by: 1. Distance between cells 2. Type of signals 5

6 Two different type of signals Neighbor cells Short and long distance cells 6

7 Mechanical signal Cell junc)on 7 htp://higheredbcs.wiley.com/legacy/college/tortora/ /

8 Biochemical signals à signal molecules Hormone Neurotransmiter Growth factor Local mediator cytokine chemokine Adipokine Myokine One cell can produce different type of signal molecules to other cells 8

9 Needed to control incoming signal and effector response CommunicaBon between cells is mediated mainly by extracellular signal molecules 9 Figure 15-1 Molecular Biology of the Cell ( Garland Science 2008)

10 Signal molecules in different cell distance Cytokine on T cell maturabon Heparan sulfate proteoglycans Short distance Long distance 10 Figure 15-4 Molecular Biology of the Cell ( Garland Science 2008)

11 Direct long distance communication Electrical impulse along the axon Faster acbon (100m/sec) Act at high local concentrabon (5x10-4 M) RelaBvely low affinity with the receptor 11 Figure 15-5b Molecular Biology of the Cell ( Garland Science 2008)

12 Indirect long distance communication The signal molecule is secreted to the blood stream Slow acbon Act at very low concentrabon (<10-8 M) Have high affinity with the receptor 12 Figure 15-4d Molecular Biology of the Cell ( Garland Science 2008)

13 Two types of signal molecules 13

14 Hydrophobic signal molecule binds to intracellular receptor 14 Figure 16-9 Essential Cell Biology ( Garland Science 2010)

15 Activated intercellular receptor involve in gene transcription regulator 15 Figure Essential Cell Biology ( Garland Science 2010)

16 Nitric Oxide (NO) pass the cell membrane and activate neighbor cell s enzyme 16 Figure Essential Cell Biology ( Garland Science 2010)

17 Hydrophilic signal molecule binds to cell- surface/transmembrane receptor 17 Figure 16-8a Essential Cell Biology ( Garland Science 2010)

18 Foreign substances that act on cell- surface receptors 18 Table 16-2 Essential Cell Biology ( Garland Science 2010)

19 How does extracellular signal can reach the inner part of the cell? Figure 16-2 Essential Cell Biology ( Garland Science 2010) Signal transduc)on (also known as cell signaling) is the transmission of molecular signals from a cell's exterior to its interior 19

20 Intracellular signal molecules 20 Figure Essential Cell Biology ( Garland Science 2010)

21 Intracellular signal molecules that play as on- off button Serine/threonin kinase Tyrosine kinase 21 Figure Essential Cell Biology ( Garland Science 2010)

22 Cell- surface receptors, three main classes 1. Ion- channel- coupled receptor 2. G- protein- coupled receptor 3. Enzyme- coupled receptor 22 Figure 16-8a Essential Cell Biology ( Garland Science 2010)

23 1. Cell surface receptor as ion- channel that transform chemical signal into electrical signal TransmiTer- gated ion channel The simplest and most direct way compare to other receptors Rapid transmission of signals across synapses in the nervous system 23 Figure 15-16a Molecular Biology of the Cell ( Garland Science 2008)

24 2. Activated G- protein- coupled receptors will activate enzyme 24 Figure 16-15b Essential Cell Biology ( Garland Science 2010)

25 G- protein coupled receptor (GPCR) Figure Essential Cell Biology ( Garland Science 2010) > 700 GPCRs in humans 25 Figure Essential Cell Biology ( Garland Science 2010)

26 The G- protein α subunit switches itself off by hydrolyzing its bound GTP The mechanism that shut off the signal off are as important as the mechanism that turn in on 26 Figure Essential Cell Biology ( Garland Science 2010)

27 G- protein coupled receptors Epinephrin ACTH FSH LH TSH Glucagon PTH Calcitonin Vasopressin rhodopsin 27

28 Some G- protein directly regulate ion channels Cause immediate change in the state and behavior of the cell e.g. Signals to slowdown heart beat 28 Figure Essential Cell Biology ( Garland Science 2010)

29 Some G- protein activate membrane- bound enzymes Involving more complex reacbon Produce addibonal intracellular signaling molecules 29 Figure Essential Cell Biology ( Garland Science 2010)

30 Enzymes activated by G protein catalyze the production of small intracellular signaling molecules The two most frequent target enzymes for G- protein Adenylyl cyclase à cyclic AMP (camp) Phospholipase C à inositol triphosphat (IP3) and diacylglycerol (DAG) 2 nd messenger 30

31 Adenylyl cyclase produces cyclic AMP (camp) from ATP camp is a second messenger 31 Figure Essential Cell Biology ( Garland Science 2010)

32 Second messenger changes enzyme activities Example: Adrenaline trigers glycogen breakdown via acbvabon of PKA (cyclic AMP- dependent protein kinase) by camp 32 Figure Essential Cell Biology ( Garland Science 2010)

33 Cellular responses mediated by camp 33 Table 16-3 Essential Cell Biology ( Garland Science 2010)

34 Active PKA also activate gene transcription 34 Figure Essential Cell Biology ( Garland Science 2010)

35 Phospholipase- C produce second messenger IP3 and DAG 35 Table 16-4 Essential Cell Biology ( Garland Science 2010)

36 Phospholipase C activates two signaling pathways; IP3 and DAG PKC: protein kinase C 36 Figure Essential Cell Biology ( Garland Science 2010)

37 3. Activated enzyme- coupled receptor will activate associated enzyme Play a role in responses to extracellular signal proteins that regulate growth, proliferabon, differenbabon and survival of the cells Act at very low concentrabon (about 10-9 to M) The response are typically slow and require many intracellular transducbon steps Figure 15-16c Molecular Biology of the Cell ( Garland Science 2008) 37

38 Receptor Tyrosine Kinase (RTK) stimulates the assembly of an intracellular signaling complex The largest class of enzyme- coupled receptors is made up by cytoplasmic domain that funcbon as tyrosine protein kinase à Receptor tyrosine kinases (RTKs) Newly phosphorylated tyrosines serve as binding site for different molecules 38 Figure Essential Cell Biology ( Garland Science 2010)

39 Receptor Tyrosine Kinase (RTK) recruits various molecule to transmit the signal to produce cellular response 39 Figure Essential Cell Biology ( Garland Science 2010)

40 Cellular response to external signal molecule can be rapid or slow 40 Figure 16-7 Essential Cell Biology ( Garland Science 2010)

41 One signal molecule induces different response on different type of cell How? 41 Figure 16-5 Essential Cell Biology ( Garland Science 2010)

42 Signal transduction pathways are interconnected 42 Figure Essential Cell Biology ( Garland Science 2010)

43 Summary Cells in mulbcellular organisms communicate through a large variety of extracellular chemical signals Small hydrophobic extracellular signals such as steroid and nitric oxide can diffuse directly across the plasma membrane Most extracellular signal molecules cannot pass through the plasma membrane Extracellular signals sbmulate a target cell when they bind to and acbvate receptor molecule There are three main classes of cell- surface receptors Ion- channel- coupled receptors G- protein- coupled receptors (GPCRs) Enzyme- coupled receptors 43

44 Summary GPCRs and enzyme- coupled receptors respond to extracellular signals by acbvabng one or more intracellular signaling pathways G- protein can directly regulate ion channels in plasma membrane acbvate/inacbvate enzyme adenylyl cyclase producing 2 nd messenger camp AcBvate/inacBvate enzyme phospholipase C producing 2 nd messenger IP3 and DAG Many enzyme- coupled receptors are receptor tyrosine kinase (RTKs) 44

45 Intercellular communication THANK YOU