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1.
Jena BP 《Experimental biology and medicine (Maywood, N.J.)》2005,230(5):307-319
Secretion occurs in all living cells and involves the delivery of intracellular products to the cell exterior. Secretory products are packaged and stored in membranous sacs or vesicles within the cell. When the cell needs to secrete these products, the secretory vesicles containing them dock and fuse at plasma membrane-associated supramolecular structures, called porosomes, to release their contents. Specialized cells for neurotransmission, enzyme secretion, or hormone release use a highly regulated secretory process. Similar to other fundamental cellular processes, cell secretion is precisely regulated. During secretion, swelling of secretory vesicles results in a build-up of intravesicular pressure, allowing expulsion of vesicular contents. The extent of vesicle swelling dictates the amount of vesicular contents expelled. The discovery of the porosome as the universal secretory machinery, its isolation, its structure and dynamics at nanometer resolution and in real time, and its biochemical composition and functional reconstitution into artificial lipid membrane have been determined. The molecular mechanism of secretory vesicle swelling and the fusion of opposing bilayers, that is, the fusion of secretory vesicle membrane at the base of the porosome membrane, have also been resolved. These findings reveal, for the first time, the universal molecular machinery and mechanism of secretion in cells. 相似文献
2.
Anderson LL 《Journal of cellular and molecular medicine》2006,10(1):126-131
The release of neurotransmitters at the nerve terminal for neurotransmission, release of insulin from beta-cells of the endocrine pancreas for regulating blood glucose levels, the release of growth hormone from GH cells of the pituitary gland to regulate body growth, or the expulsion of zymogen from exocrine pancreas to digest food, are only a few examples of key physiological processes made possible by cell secretion. It comes as no surprise that defects in cell secretion are the cause for numerous diseases, and have been under intense investigation for over half century. Only in the last decade, the molecular machinery and mechanism of cell secretion has become clear. Cell secretion involves the docking and transient fusion of membrane-bound secretory vesicles at the base of plasma membrane structures called porosomes, and the regulated expulsion of intravesicular contents to the outside, by vesicle swelling. The discovery of the porosome in live cells, its morphology and dynamics at nanometer resolution and in real time, its isolation, its composition, and its structural and functional reconstitution in lipid membrane, are complete. The molecular mechanism of secretory vesicle fusion at the base of porosomes, and the regulated expulsion of intravesicular contents during cell secretion, are also resolved. In this minireview, the monumental discovery of the porosome, a new cellular structure at the cell plasma membrane, is briefly discussed. 相似文献
3.
Jeftinija S 《Journal of cellular and molecular medicine》2006,10(2):273-279
Cell secretion has come of age, and a century old quest has been elegantly solved. We have come a long way since earlier observations of what appeared to be 'fibrillar regions' at the cell plasma membrane, and electrophysiological studies suggesting the presence of 'fusion pores' at the cell plasma membrane where secretion occurs. Finally, the fusion pore or 'porosome' has been discovered, and its morphology and dynamics determined at nm resolution and in real time in live secretory cells. The porosome has been isolated, its composition determined and it has been both structurally and functionally reconstituted in artificial lipid membrane. The discovery of the porosome as the universal secretory machinery in cells and the discovery of the molecular mechanism of vesicular content expulsion during cell secretion have finally enabled a clear understanding of this important cellular process. This review outlines the fascinating and exciting journey leading to the discovery of the porosome, ultimately solving one of the most difficult, significant, and fundamental cellular process -cell secretion. 相似文献
4.
Porosomes are the universal secretory portals at the cell plasma membrane, where membrane-bound secretory vesicles transiently dock and fuse to expel intravesicular contents to the outside during cell secretion. In the past decade, the neuronal porosome complex, a 10-15nm cup-shaped lipoprotein structure has been isolated, its partial composition and 3D contour map determined, and it has been functionally reconstituted into artificial lipid membrane. Here we further determine the composition of the neuronal porosome proteome using immunoisolation and gel filtration chromatography, followed by tandem mass spectrometry. Results from the study demonstrate nearly 40 proteins to constitute the neuronal porosome proteome. Furthermore, interaction of proteins within the porosome and their resulting arrangement is predicted. The association and dissociation of proteins at the porosome following stimulation of cell secretion demonstrate the dynamic nature of the organelle. 相似文献
5.
‘Porosome’ discovered nearly 20 years ago provides molecular insights into the kiss‐and‐run mechanism of cell secretion
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Bhanu P. Jena 《Journal of cellular and molecular medicine》2015,19(7):1427-1440
Secretion is a fundamental cellular process in living organisms, from yeast to cells in humans. Since the 1950s, it was believed that secretory vesicles completely merged with the cell plasma membrane during secretion. While this may occur, the observation of partially empty vesicles in cells following secretion suggests the presence of an additional mechanism that allows partial discharge of intra‐vesicular contents during secretion. This proposed mechanism requires the involvement of a plasma membrane structure called ‘porosome’, which serves to prevent the collapse of secretory vesicles, and to transiently fuse with the plasma membrane (Kiss‐and‐run), expel a portion of its contents and disengage. Porosomes are cup‐shaped supramolecular lipoprotein structures at the cell plasma membrane ranging in size from 15 nm in neurons and astrocytes to 100–180 nm in endocrine and exocrine cells. Neuronal porosomes are composed of nearly 40 proteins. In comparison, the 120 nm nuclear pore complex is composed of >500 protein molecules. Elucidation of the porosome structure, its chemical composition and functional reconstitution into artificial lipid membrane, and the molecular assembly of membrane‐associated t‐SNARE and v‐SNARE proteins in a ring or rosette complex resulting in the establishment of membrane continuity to form a fusion pore at the porosome base, has been demonstrated. Additionally, the molecular mechanism of secretory vesicle swelling, and its requirement for intra‐vesicular content release during cell secretion has also been elucidated. Collectively, these observations provide a molecular understanding of cell secretion, resulting in a paradigm shift in our understanding of the secretory process. 相似文献
6.
Jena BP 《Journal of cellular and molecular medicine》2004,8(1):1-21
Secretion and membrane fusion are fundamental cellular processes involved in the physiology of health and disease. Studies within the past decade reveal the molecular mechanism of secretion and membrane fusion in cells. Studies reveal that membrane-bound secretory vesicles dock and fuse at porosomes, which are specialized plasma membrane structures. Swelling of secretory vesicles result in a build-up of intravesicular pressure, which allows expulsion of vesicular contents. The discovery of the porosome, its isolation, its structure and dynamics at nm resolution and in real time, its biochemical composition and functional reconstitution, are discussed. The molecular mechanism of secretory vesicle fusion at the base of porosomes, and vesicle swelling, have been resolved. With these findings a new understanding of cell secretion has emerged and confirmed by a number of laboratories. 相似文献
7.
Porosomes are the universal secretory machinery of the cell plasma membrane, where membrane-bound secretory vesicles transiently dock and fuse to expel intravesicular contents to the environment during cell secretion. In neurons, 12- to 17-nm cup-shaped lipoprotein structures possessing a central plug are present at the presynaptic membrane, where 40-50 nm in diameter synaptic vesicles transiently dock and fuse to release neurotransmitters. The neuronal porosome complex has been isolated, its composition determined and it has been both structurally and functionally reconstituted in artificial lipid membranes. Earlier studies using AFM (atomic force microscopy), EM (electron microscopy), electron density and 3D contour mapping provide the structure and assembly of proteins within the neuronal porosome complex at the nanoscale level. A set of eight protein units lining the neuronal porosome cup is present, each connected via spoke-like elements to a central plug, hypothesized for the rapid opening and closing of the structure to the outside. In the present study, ultrahigh-resolution imaging of the presynaptic membrane of isolated synaptosome preparations demonstrate, for the first time, the presence of neuronal porosomes in both their open and close conformations. The results suggests that the central plug is retracted into the porosome cup in its open conformation and pushed outward to seal the porosome opening, supporting the hypothesis that it operates as the opening-closing device of the complex. 相似文献
8.
Lee JS Cho WJ Jeftinija K Jeftinija S Jena BP 《Journal of cellular and molecular medicine》2009,13(2):365-372
Secretion is a universal cellular process occurring in bakers yeast, to the complex multicellular organisms, to humans beings. Neurotransmission, digestion, immune response or the release of hormones occur as a result of cell secretion. Secretory defects result in numerous diseases and hence a molecular understanding of the process is critical. Cell secretion involves the transport of vesicular products from within cells to the outside. Porosomes are permanent cup-shaped supramolecular structures at the cell plasma membrane, where secretory vesicles transiently dock and transiently fuse to release intravesicular contents to the outside. In the past decade, porosomes have been determined to be the universal secretory machinery in cells, present in the exocrine pancreas, endocrine and neuroendocrine cells, and in neurons. In this study, we report for the first time the presence of porosomes in rat brain astrocytes. Using atomic force microscopy on live astrocytes, cup-shaped porosomes measuring 10–15 nm are observed at the cell plasma membrane. Further studies using electron microscopy confirm the presence of porosomes in astrocytes. Analogous to neuronal porosomes, there is a central plug in the astrocyte porosome complex. Immunoisolation and reconstitution of the astrocyte porosome in lipid membrane, demonstrates a structure similar to what is observed in live cells. These studies demonstrate that in astrocytes, the secretory apparatus at the cell plasma membrane is similar to what is found in neurons. 相似文献
9.
A new cell structure--"porosome", discovered by the American scientist Bhanu Jena and co-wokers, is described. Mechanisms of budding and fusion of transport vesicle are elucidated in addition to those of fusion of secretory vesicles at the cell plasma membrane, and of release of intravesicular contents. The morphology of porosomes, their contents and functional reconstruction in lipid bilayer membranes were examined at a near nanometer resolution. Using atomic force microscopy, the presence of circular "pits", measuring 400-1200 nm in diameter with small 100-150 nm wide "depressions" inside and 3-4 deep pores, called porosomes, was demonstrated. A porosome is cup-shaped and 15-30 nm wide. Porosomes are the places where secretory vesicles fuse with the plasma cell membrane, and where the intravesicular content is released. 相似文献
10.
It is well established that during cell secretion, membrane-bound secretory vesicles dock and fuse at the base of supramolecular
cup-shaped structures at the cell plasma membrane called “porosomes”, to expel intra-vesicular contents to the outside. In
neurons, it has been demonstrated that 12–17 nm cupshaped lipoprotein structure possessing a central plug are present at the
presynaptic membrane, where 50 nm in diameter synaptic vesicles transiently dock and fuse to release neurotransmitters. In
the past decade, the neuronal porosome has been isolated and its major chemical composition determined. Additionally, the
porosome has been both structurally and functionally reconstituted into artificial lipid membrane, establishing its role as
the secretory portal in neurons. Studies utilizing atomic force and electron microscopy, combined with electron density and
3D contour mapping, provide at the nanoscale, the structure and assembly of proteins within the neuronal porosome. In the
current study, ultrahigh resolution imaging of the presynaptic membrane of isolated brains from both rats and cats, demonstrate
for the first time, the presence of neuronal porosomes in cat brain, and further confirms the presence of porosomes at the
presynaptic membrane in rat brain synaptosomes. Results from the present study further confirm the cup-shaped morphology of
porosomes in the rat brain, and demonstrates their similar shape and size in the cat nerve terminal. The study also demonstrates
for the first time, the universal presence of similar porosomes in different species of mammals. 相似文献
11.
It is well established that during cell secretion, membrane-bound secretory vesicles dock and fuse at the base of supramolecular cup-shaped structures at the cell plasma membrane called "porosomes", to expel intra-vesicular contents to the outside. In neurons, it has been demonstrated that 12-17 nm cup-shaped lipoprotein structure possessing a central plug are present at the presynaptic membrane, where 50 nm in diameter synaptic vesicles transiently dock and fuse to release neurotransmitter. In the past decade, the neuronal porosome has been isolated and its major chemical composition determined. Additionally, the porosome has been both structurally and functionally reconstituted into artificial lipid membrane, establishing its role as the secretory portal in neurons. Studies utilizing atomic force and electron microscopy, combined with electron density and 3D contour mapping, provide at the nanoscale, the structure and assembly of proteins within the neuronal porosome. In the current study, ultrahigh resolution imaging of the presynaptic membrane of isolated brains from both rats and cats, demonstrate for the first time, the presence of neuronal porosomes in cat brain, and further confirms the presence of porosomes at the presynaptic membrane in rat brain synaptosomes. Results from the present study further confirm the cup-shaped morphology of porosomes in the rat brain, and demonstrates their similar shape and size in the cat nerve terminal. The study also demonstrates for the first time, the universal presence of similar porosomes in different species of mammals. 相似文献
12.
Using the optical microscope, real adventures in cellular research began in earnest in the latter half of the nineteenth century. With the development of the electron microscope, ultramicroscopy, and improved cell staining techniques, significant advances were made in defining intracellular structures at the nanometer level. The invention of force microscopy, the atomic force microscope (AFM) in the mid 1980s, and the photonic force microscope (PFM) in the mid 1990s, finally provided the opportunity to study live cellular structure-function at the nanometer level. Working with the AFM, dynamic cellular and subcellular events at the molecular level were captured in the mid 1990s, and a new cellular structure 'the porosome' in the plasma membrane of all secretory cells has been defined, where specific docking and fusion of secretory vesicles occur. The molecular mechanism of fusion of the secretory vesicle membrane at the base of the porosome membrane in cells, and the regulated release of intravesicular contents through the porosome opening to the extracellular space, has been determined. These seminal discoveries provide for the first time a molecular mechanism of cell secretion, and the possibility to ameliorate secretory defects in disease states. 相似文献
13.
The astrocyte porosome complex, the secretory machinery at the plasma membrane of astrocytes, is a 10-15 nm cup-shaped lipoprotein structure possessing a central plug. Since the porosome is a membrane-associated, multi-protein complex, it has precluded the generation of 3D crystals for X-ray diffraction studies, nor structural analysis at the atomic level using the solution NMR. These limitations were partially overcome in the current studies, furthering our understanding of the porosome structure in astrocytes. Using atomic force microscopy, electron microscopy, and electron density and 3D contour mapping, finally provides at the nanoscale, the structure and assembly of proteins within the astrocyte porosome complex. Results from this study demonstrate a set of protein units lining the porosome cup, each connected via spoke-like elements to a central plug region within the structure. In contrast to the neuronal porosome, which possess eight globular proteins at the outer rim of the complex, the porosome complex appear to possess 12 such globular structures. Nature has designed the porosome as the universal secretory machinery, but has fine-tuned its use to suite secretion from different cell types. The isolation of intact astrocyte porosomes for near-atomic resolution using cryo-electron diffraction measurements, is finally possible. 相似文献
14.
Cup‐shaped lipoprotein structures called porosomes are the universal secretory portals at the cell plasma membrane, where secretory vesicles transiently dock and fuse to release intravesicular contents. In neurons, porosomes measure ~15 nm and are comprised of nearly 40 proteins, among them SNAREs, ion channels, the Gαo G‐protein and several structural proteins. Earlier studies report the interaction of specific lipids and their influence on SNAREs, ion channels and G‐protein function. Our own studies demonstrate the requirement of cholesterol for the maintenance of neuronal porosome integrity, and the influence of lipids on SNARE complex assembly. In this study, to further understand the role of lipids on porosome structure‐function, the lipid composition of isolated neuronal porosome was determined using mass spectrometry. Using lipid‐binding assays, the affinity of porosome‐associated syntaxin‐1A to various lipids was determined. Our mass spectrometry results demonstrate the presence of phosphatidylinositol phosphates (PIP's) and phosphatidic acid (PA) among other lipids, and the enriched presence of ceramide (Cer), lysophosphatidylinositol phosphates (LPIP) and diacylglycerol (DAG). Lipid binding assays demonstrate the binding of neuronal porosome to cardiolipin, and confirm its association with PIP's and PA. The ability of exogenous PA to alter protein–protein interaction and neurotransmitter release is further demonstrated from the study. 相似文献
15.
Landmark discoveries in intracellular transport and secretion 总被引:1,自引:1,他引:0
Paknikar KM 《Journal of cellular and molecular medicine》2007,11(3):393-397
Cellular protein transport and secretion is fundamental to the very existence of an organism, regulating important physiological functions such as reproduction, digestion, energy production, growth, neurotransmission, hormone release, water and ion transport, etc., all required for the survival and maintenance of homeostasis within an organism. Molecular understanding of transport and secretion of intracellular product has therefore been of paramount importance and aggressively investigated for over six decades. Only in the last 20 years, the general molecular mechanism of the process has come to light, following discovery of key proteins involved in ER-Golgi transport, and discovery of the porosome the universal secretion machinery in cells. 相似文献
16.
Bhanu P. Jena Sang-Joon Cho Aleksandar Jeremic Marvin H. Stromer Rania Abu-Hamdah 《Biophysical journal》2003,84(2):1337-1343
Earlier studies using atomic force microscopy (AFM) demonstrated the presence of fusion pores at the cell plasma membrane in a number of live secretory cells, revealing their morphology and dynamics at nm resolution and in real time. Fusion pores were stable structures at the cell plasma membrane where secretory vesicles dock and fuse to release vesicular contents. In the present study, transmission electron microscopy confirms the presence of fusion pores and reveals their detailed structure and association with membrane-bound secretory vesicles in pancreatic acinar cells. Immunochemical studies demonstrated that t-SNAREs, NSF, actin, vimentin, α-fodrin and the calcium channels α1c and β3 are associated with the fusion complex. The localization and possible arrangement of SNAREs at the fusion pore are further demonstrated from combined AFM, immunoAFM, and electrophysiological measurements. These studies reveal the fusion pore or porosome to be a cup-shaped lipoprotein structure, the base of which has t-SNAREs and allows for docking and release of secretory products from membrane-bound vesicles. 相似文献
17.
Cholesterol has been proposed to play a critical role in regulating neurotransmitter release and synaptic plasticity. The neuronal porosome/fusion pore, the secretory machinery at the nerve terminal, is a 12-17 nm cup-shaped lipoprotein structure composed of cholesterol and a number of proteins, among them calcium channels, and the t-SNARE proteins Syntaxin-1 and SNAP-25. During neurotransmission, synaptic vesicles dock and fuse at the porosome via interaction of their v-SNARE protein with t-SNAREs at the porosome base. Membrane-associated neuronal t-SNAREs interact in a circular array with liposome-associated neuronal v-SNARE to form the t-/v-SNARE ring complex. The SNARE complex along with calcium is required for the establishment of continuity between opposing bilayers. Here we show that although cholesterol is an integral component of the neuronal porosome and is required for maintaining its physical integrity and function, it has no influence on the conformation of the SNARE ring complex. 相似文献
18.
The involvement of secretory vesicle swelling has been proposed in secretion; however, little is known about its role. Using both the pancreatic acinar cell and neuronal model, we show secretory vesicle swelling in live cells. Our study reveals that vesicle swelling potentiates its fusion at the cell plasma membrane, and is required for expulsion of intravesicular contents. Since the extent of swelling is directly proportional to the amount of vesicular contents expelled, this provides cells with the ability to regulate release of secretory products. These direct observations of the requirement of secretory vesicle swelling in secretion, provides an understanding of the appearance of partially empty vesicles following the process. 相似文献
19.
During secretion, membrane-bound secretory vesicles dock and fuse at the base of porosomes in the cell plasma membrane. Among other proteins, the porosome is composed of SNAREs and Ca2+-channels. Ca2+-channels and SNAREs have been implicated in cell secretion. Several immunoprecipitation and binding studies suggest the physical interaction of the t-SNARE proteins, Syntaxin-1 and SNAP-25 with various Ca2+-channels. In this study, using yeast two-hybrid and immunoanalysis, we demonstrate for the first time, direct interaction of SNAP-23 and a L-type Ca2+-channel at the plasma membrane in pancreas. 相似文献
20.
Secretion machinery at the cell plasma membrane 总被引:1,自引:0,他引:1
Jena BP 《Current opinion in structural biology》2007,17(4):437-443
Secretion is a fundamental cellular process involving the regulated release of intracellular products from cells. Physiological functions such as neurotransmission, or the release of hormones and digestive enzymes, are all governed by cell secretion. Three critical activities occur at the cell plasma membrane to ensure secretion. Membrane-bound secretory vesicles dock, fuse, and expel their contents to the outside via specialized and permanent plasma membrane structures, called porosomes or fusion pores. In recent years, significant progress has been made in our understanding of these three key cellular activities required for cell secretion. The molecular machinery and mechanism involving them is summarized in this article. 相似文献