Advanced Concepts and Perspectives of Membrane Physics
Highly effective pathways of transmembrane signal transmission are realized by functional membrane domain formation through logistically controlled recruitment of functional proteins to specific sites on cytoplasmic membrane leaflets. Sites of assembly are selected by priming membranes through master switches generating local swarms of super affinity lipid anchors, such as PI(3,4,5)P3 and diacylglycerol (DAG).
Formation and activation of functional domains are regulated by agonistically or antagonistically cooperating molecular switches. We consider here the agonistic Rab4/Rab 5 tandem, serving the rapid receptor recycling, and the antagonistic pair of GTPases Rac-1 and Rho A, controlling the state of the actin cortex. To avoid over-excitations of cells (implying the danger of tumorigenesis), the omnipresent phosphoinositide anchors are protected by layers of the polybasic protein MACKS recruited by electrostatic-hydrophobic forces.
The universality of cell control systems is exemplified by the observation that extrinsic forces and hormones can trigger the generation of very similar types of transmembrane signal transmission centers assembled around receptor tyrosine kinases (RTK). These signal amplifying domains can regulate cellular membrane processes simultaneously through fast biochemical signals, eliciting the rapid structural change of the composite cell envelope, and slow, genetically controlled processes for adapting the mechanical impedances of cells and tissues.
Membrane-based reactions can be controlled via the access of reaction spaces by constituents or enzymes. They can be regulated over large distances by contacting distant membranes through synaptic contacts (such as endoplasmic and of immunological synapses).
Hopefully, insights in the analogy of technical and biological control mechanism may teach us how to generate new self-healing composite materials in logistic ways.
KeywordsFunctional membrane domain formation Membrane-associated protein recruitment by electrostatic hydrophobic forces Transmembrane signal amplifying domains MARCKS protein-controlled membrane processes Reticulons controlled tubular membrane networks Immunological and endoplasmic synapses
Guanine hydrolyzing protein accelerating the deactivation of GTPase
Guanine exchange factor accelerating the activation of GTPases by replacement of GDP by GTP
Guanine exchange inhibitor that maintains GTPases in the resting state
- P(4,5)P2, P(3,4,5)P3
Phosphoinositol (4,5)-diphosphate, Phosphatidylinositol (3,4,5)-trisphosphate
Protein kinase C, a regulator of filopoida formation
Protein kinase 3 that catalyzes the phosphorylation of the 3′-OH position on the inositol ring
Phospholipase gamma, the generator of DAG lipids
Financial support by the Excellence Program of the Technical University of Munich and by the Lehrstuhl für Angewandte Physik of the Ludwig Maximilian University is gratefully acknowledged.
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