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1 Lecture 24: Cellular Signaling and adhesion Reading: Alberts Ch 16, Pollard Chapter 24, and Phillips Ch 19.4 and Science News and Views article MWC model for Chemotaxis pathway On = CheY-P; Off = CheY 1
2 Two-component signaling pathway Methylation + CheR and CheB add memory of past concentrations 2
3 Cooperativity is also important 3
4 Adhesion proteins generate both mechanical force and cell signaling 4
5 Cell-cell adhesion machinery Pearson Education Cadherin molecule shape homotypic cadherin dimer 5
6 How does cadeherin interact with actin? William I. Weis, and W. James Nelson J. Biol. Chem. 2006;281: The American Society for Biochemistry and Molecular Biology, Inc. At least 3 roles for cadherins in cellcell adhesion 1.Adhesion tension Maitre and Heisenberg. Current Biology,
7 At least 3 roles for cadherins in cell-cell adhesion 2. Adhesion signaling Maitre and Heisenberg. Current Biology, 2013 At least 3 roles for cadherins in cell-cell adhesion 3. Adhesion coupling Maitre and Heisenberg. Current Biology,
8 Implications for development Zebrafish development 8
9 Surface tension could be important for biological function animal shield stage : mesendoderm cells move upward, ectoderm cells move downward vegetal Self-organization of tissue 9
10 Surface tension varies between cell types animal vegetal E.-M. Schoetz thesis tissue N (total) σ (dyne/cm) Mesendoderm ± 0.04 MZoep (Ecto) ± 0.06 Lefty (Ecto) ± 0.07 Why fluids have surface tension Fluid molecules like to stick together. Surface molecules have fewer neighbors Surface tension proportional to stickiness liquid interface 10
11 Differential Adhesion Hypothesis (DAH) Steinberg flow arise[s] from tissue surface tensions that in turn arise from differences in intercellular adhesiveness Lecuit and Lenne Definition: surface tension difference in mechanical energy (D W) between a surface cell and an interior cell, times the number of cells per unit surface area liquid interface cell-medium interface 11
12 But, there is a paradox 12
13 Possible resolution: Mechanics Cadherin bonds Signaling Extracellular signals Cortical actomyosin Initial contact < 1 min Cell-cell adhesion (Cadherin-cadherin interactions) Rho GTPases Local changes in actomyosin contractility Mature contact > 1-10 min Mechanical polarization Fig. 1. Mechanical polarization in cell doublets. Initially, two cells coming into con- Effect of cadherin signaling on tissue cohesion A Cell culture medium B C Cortical actomyosin Cadherin bonds Fig. 2. Mechanical polarization at tissue-culture and tissue-tissue boundaries. magnitude of TST in vitro. (B and C) Nuclei are labeled blue or orange to 13
14 Extra information about membranes. Signaling Mechanisms- Membrane Receptors, Transduction and Second Messengers 14
15 Classes of Receptors We will focus on 3 here: Pollard Figure 24-1 (1) G-Protein Coupled Receptors 15
16 Example: Activated GPCR activates G proteins by GDP -> GTP exchange (2) Ion channel receptors 16
17 (3) Receptor tyrosine kinases (RTKs) and example for enzyme coupled receptors Example: RTKs activate Ras 17
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