1. Simon Danisch

2. Introduction little is known about the influence of the membrane surface environment on the behavior of proteins membranes are difficult to study in vitro and in vivo current knowledge of the role of the membrane in signal transduction is just a glimmer of a much larger story

3. Membrane physical chemistry membranes provide physical surfaces adsorbtion of molecular reactants increase their relative probability of an encounter (reaction kinetics) the membrane is not a homogenous fluid it is a nanometer-scale emulsion of lipids, cholesterol and proteins in intimate association with the cortical cytoskeleton

4. Membrane physical chemistry in the membrane are composition fluctuations (membrane rafts) lipids and cholesterol show miscibility phase transition and critical-point phenomena at physiological temperatures membranes are fluid in two dimensions but elastic in the third dimension allostery at a distance for juxtacrine signaling

5. Protein Kinase C (PKC) isozymes inactive PKC is associated with HSP90 activation of the receptor lead to production of DAG and an increase of cytoplasmic Ca 2+ PKC is primed for activation by phosphorylation by PDK1 and mTORc C1 binds to DAG and C2 to PIP2 PKC is recruited to the membrane and allosteric activated  „coincidence detection“

6. Self-organisation of Min proteins on the membrane Min proteins are bacterial proteins which are crucial for cell division and undergo spatiotemporal oscillations in vivo MinD and MinE spontaneously organize into propagating wave pattern on supported membrane surfaces in vitro in presence of ATP  dynamic spatial organisiation could be involved in a wide range of signaling processes

7. Activation of RAS by SOS at the membrane Textbook model activation of the growth factor receptor recruitment of the cytosolic SOS to the membrane activation of RAS by SOS

8. Recruitment of SOS to the membrane colocalization at the membrane can increase the local concentration by a factor of 1000 this effect only occur if both molecules are localized at the same membrane if only one protein is membrane anchored, then dissociation of the complex will lead to rapid diffusion away from the membrane  multiple membrane attachment points

9. SOS has two binding sites for RAS one binding site for RAS-GTP and one for RAS-GDP binding to the RAS-GTP site activates the catalytic module of SOS RAS is a allosteric activator of SOS the activity of SOS depends on the surface density of RAS molecules rather than the bulk concentration

10. a DH-PH module blocks the allosteric RAS binding site and prevents uncontrolled activation binding of PH and H to PIP2 and SOS to the activated receptor likely leads to SOS activation

11. EphA2 receptor tyrosine kinase triggering by ephrin-A1 Ephrins are activating ligands for Eph receptors Both are membrane anchored and act in a juxtacrine manner numerous spatial and mechanical aspects of both membranes have a direct impact on the receptor-ligand -interaction

12. EphA2 receptor tyrosine kinase triggering by ephrin-A1 there is a step in the signaling cascade that is sensitive to the large- scale spatial mutation of EphA2 or possibly even the tensile forces acting on them

13. Activation of actin nucleation by WASP WASP is a actin nucleation- promoting factor WASP is intrinsically inactive Phosphorylation primes the complex for interaction with the membrane WASP binds to PIP3 finally binding to PIP3 and Rac- GTP activates WASP and lead to actin nuleation

14. Conclusion the knowlege how the membrane is involved in signalling is still at the begining membrane composition plays a importent role in signal transduction through the membrane

15. Thank you