Membranous compartments within cells form not only an aesthetically interesting, dynamical three-dimensional structure—they also present a conundrum: how do these exotic vesicular, tubular, and interconnected pancake-like shapes meld into each other and communicate, yet maintain distinct identities and morphologies, in addition to controlling the trafficking and precise targeting of their cargoes? How are they themselves regulated in size, shape, and positioning in the cell—all of which seem to be of prime importance to functioning?
Defects in membrane trafficking can be disastrous for the cell and for the organism. Diseases as diverse as Parkinson’s, diabetes, metabolic syndrome, and cancer are known to have at least some causal component, if not a central origin, related to vesicle trafficking and/or lipid metabolic control. An expanding array of possible causes and consequences of faulty trafficking among vesicular compartments is being catalogued, with ever more surprising connections being discovered. While it is clear that the endocytic targeting and regulation of growth receptors and intracellular signaling molecules, as well as degradation of toxic, misfolded, or otherwise harmful proteins would be critical to health of the tissue and organism, other functions mediated by vesicular membranes are less obvious. Endoplasmic reticulum (ER)- and oxidative-stress related mechanisms turn out to control not only protein turnover, but also tissue formation and morphology. Various vesicular organelles which were thought to function as more or less independent entities have now been observed—often with the help of the newest wave of high-resolution imaging techniques—in the act of intimate contact and lipid exchange. ER-mitochondrial contacts were an early example of such conduits of transport, but now nearly all possible pairings among ER, late endosome, plasma membrane, mitochondria, lysosomes, and the nuclear membrane have been witnessed and their purposes described.
Mechanisms implicated in controlling pathway targeting and vesicle dynamics have come from surprising sources. Recent scenarios have invoked entropy as a controlling force in the fusion of early endocytic compartments, friction in scission of tubular vesicles, and adhesion complexes in membrane allocation and recycling. Various observations hint that seemingly far-flung cellular components exert unexpected effects on each other: lipid droplets in the distribution of histone cargoes to the nucleus; membrane adhesion complexes in the control of vesicle dynamics from afar, via a Rube Goldberg-machine of cytoskeleton, motors, kinases, and accessory proteins—all interacting in some way with phosphoinositides.
Membrane biophysics and dynamics are important determinants of vesicular behavior and have accordingly been a subject of keen interest. Many questions concern the influence of lipid composition, curvature, and specific lipid species on membrane dynamics, and how these either control or are controlled by membrane sub-domains. One area that will surely break into this realm of study in a big way is the influence of metabolic factors like diet and oxidative stress. Physical membrane properties that relate to dynamics, such as tension, pressure, composition and fluidity, can now be monitored or even manipulated using exciting technologies such as laser tweezers or cutting, various types of optical spectroscopy, lipid uncaging, fluorescent sensors, and high-resolution live imaging.
The questions abound—as do the methods and model systems used to address these. An exciting sampling of some of these will be presented in this Research Topic on connections to vesicle trafficking.
Membranous compartments within cells form not only an aesthetically interesting, dynamical three-dimensional structure—they also present a conundrum: how do these exotic vesicular, tubular, and interconnected pancake-like shapes meld into each other and communicate, yet maintain distinct identities and morphologies, in addition to controlling the trafficking and precise targeting of their cargoes? How are they themselves regulated in size, shape, and positioning in the cell—all of which seem to be of prime importance to functioning?
Defects in membrane trafficking can be disastrous for the cell and for the organism. Diseases as diverse as Parkinson’s, diabetes, metabolic syndrome, and cancer are known to have at least some causal component, if not a central origin, related to vesicle trafficking and/or lipid metabolic control. An expanding array of possible causes and consequences of faulty trafficking among vesicular compartments is being catalogued, with ever more surprising connections being discovered. While it is clear that the endocytic targeting and regulation of growth receptors and intracellular signaling molecules, as well as degradation of toxic, misfolded, or otherwise harmful proteins would be critical to health of the tissue and organism, other functions mediated by vesicular membranes are less obvious. Endoplasmic reticulum (ER)- and oxidative-stress related mechanisms turn out to control not only protein turnover, but also tissue formation and morphology. Various vesicular organelles which were thought to function as more or less independent entities have now been observed—often with the help of the newest wave of high-resolution imaging techniques—in the act of intimate contact and lipid exchange. ER-mitochondrial contacts were an early example of such conduits of transport, but now nearly all possible pairings among ER, late endosome, plasma membrane, mitochondria, lysosomes, and the nuclear membrane have been witnessed and their purposes described.
Mechanisms implicated in controlling pathway targeting and vesicle dynamics have come from surprising sources. Recent scenarios have invoked entropy as a controlling force in the fusion of early endocytic compartments, friction in scission of tubular vesicles, and adhesion complexes in membrane allocation and recycling. Various observations hint that seemingly far-flung cellular components exert unexpected effects on each other: lipid droplets in the distribution of histone cargoes to the nucleus; membrane adhesion complexes in the control of vesicle dynamics from afar, via a Rube Goldberg-machine of cytoskeleton, motors, kinases, and accessory proteins—all interacting in some way with phosphoinositides.
Membrane biophysics and dynamics are important determinants of vesicular behavior and have accordingly been a subject of keen interest. Many questions concern the influence of lipid composition, curvature, and specific lipid species on membrane dynamics, and how these either control or are controlled by membrane sub-domains. One area that will surely break into this realm of study in a big way is the influence of metabolic factors like diet and oxidative stress. Physical membrane properties that relate to dynamics, such as tension, pressure, composition and fluidity, can now be monitored or even manipulated using exciting technologies such as laser tweezers or cutting, various types of optical spectroscopy, lipid uncaging, fluorescent sensors, and high-resolution live imaging.
The questions abound—as do the methods and model systems used to address these. An exciting sampling of some of these will be presented in this Research Topic on connections to vesicle trafficking.