Membrane trafficking

Abstract

Life is inevitably coupled to the existence of lipid bilayers. Biological membranes provide physical barriers that permit selective material transfer and signal perception and transmission. Simple cells, such as bacteria, are surrounded by a single membrane; eukaryotic cells contain numerous structurally and functionally distinct compartments. In order to propagate these compartments or to transport cargo between them, membranes undergo periodic fission/fusion events. A broad variety of physiological events, such as cell/organelle reproduction, fertilization, neurotransmission, muscle formation, and virus infection, are dependent on membrane fission/fusion processes. This raises the major question as to which molecular mechanisms and machineries mediate these membrane trafficking processes. For example, in vesicular transport the budding and fusion of a transport vesicle poses the following problems: How are budding sites selected? Do protein scaffolds and/or lipids shape the membrane? Do such scaffolds “push” or “pull” membranes into shape? How is the cargo and transport machinery packaged into a nascent vesicle? Is vesicle formation intimately linked to vectorial transport along the cytoskeleton? How are vesicles uncoated? How do vesicles recognize and fuse with the target membrane? Which spatial and temporal mechanisms control membrane fusion? Which roles do the cytoskeleton and/or local lipid remodeling play in the fusion process? How is the transport machinery recycled? Which steps provide the energy to drive the overall process? These and related topics are addressed in this FEBS Letters Special Issue by experts in the field of membrane trafficking. To gain a comprehensive overview about membrane fission and fusion, the Minireviews cover various research fields including intracellular transport processes in the endocytic and secretory pathway, chloroplast division, mitochondrial fusion, viral budding and fusion, cell–cell fusion events, lipid microdomains and phosphoinositide metabolism. Considering the broad variety of physiological processes it is not surprising that nature makes use of different machineries and mechanisms to accomplish the goal of propagating or merging lipid bilayers. Nevertheless, some recurrent themes appear. One is the use of small GTP-binding proteins as molecular switches or mechanical devices to locally control fission and fusion processes (Sar1/Arf family members control vesicle budding, dynamin-related proteins mediate certain types of vesicle and organelle fission processes, Rab proteins locally regulate membrane targeting/tethering, Rho/Cdc42 family members control the cytoskeleton and tethering machinery). Another general principle seems to be the use of hairpin structures, which assemble in a directional zipper-like fashion to bring membranes in close apposition, finally culminating in membrane fusion. However, whether this mechanism, used in intracellular transport and viral fusion, is also directly applicable to cell-to-cell fusion still remains to be explored. It seems that, whether we consider membrane fission or fusion, distinct core machineries do the main job and ‘add-on’ components control the overall process. These ‘add-on’ components ensure the exquisite temporal and spatial regulation that is necessary to maintain the compartmental integrity of a cell and to build complex organisms. I would like to thank all my colleagues who invested their precious time to contribute Minireviews or helped as anonymous reviewers. I am grateful to Patricia McCabe and Anne Müller at FEBS Letters, and Martina Franke–Schaub, my secretary, for their continuous support, insightful comments, and managing skills, which were critical in preparing this Special Issue. Finally, I hope that this issue will be helpful to reveal to a large audience molecular insights of the distinct mechanisms and machineries that nature employs to manage membrane fission and fusion processes in a coordinated fashion.