CHEMOTAXIS Signalling the way forward unimuenchen趋化信号途径慕尼黑大学.ppt

Hauptseminar Biophysik der Systeme: Chemotaxis CHEMOTAXIS:Signalling the way forward Christian Westermeier Chemotaxis of Dictyostelium discoideum Structure of the presentation short introduction signalling pathways: - directional sensing - establishment of polarity - locomotion of the cell summarization Chemotaxis Some types of cells can sense the presence of extracellular signals and guide their movement in the direction of the concentration gradient Problem: Hit the Target(…or “Jack, the lonely cell”) uniform cell is attracted by a destination Problem: Hit the Target(…or “Jack, the lonely cell”) uniform cell is attracted by a destination Problem: Hit the Target(…or “Jack, the lonely cell”) 1. Directional Sensing Orientation Information: spatial ?? temporal Chemoattractants set directions Dicties undergo directed cell migration in response to nutrients platelet-activating-factor (PAF) cAMP Detection of Ligands Receptors in the membrane of the cell (4 different ones for cAMP) seven-transmembrane-spanning receptors couple to heterotrimeric G proteins + also directly to downstream events (G-protein independent) G proteins in Dicties complex of α-,β-,γ-subunit only one β-subunit and one γ-subunit exist βγ-complex essential for chemotaxis 11 different α-subunits (45% identical) Gα2 mainly linked to cAMP-receptors Receptors coupled to G-proteins Localization of receptors Problem: Hit the Target(…or “Jack, the lonely cell”) 2. Polarization Polarity response to a detected spatial gradient: extension of the cell membrane ? pseudopod formation at the leading edge + suppression of lateral pseudopods elsewhere + retraction of the uropod at the rear of the cell absence of chemoattractants presence of chemoattractants biochemical + functional polarization front of the cell (leading edge): contains actin filaments ? induce formation of new pseudopodia (only one at a time) back of the cell (uropod): contains myosin filaments ? retracting the uropod Phosph