Neuronal porosome lipidome

Lewis, Kenneth T.; Maddipati, Krishna Rao; Taatjes, Douglas J.; Jena, Bhanu P.

doi:10.1111/jcmm.12383

Cited by 15 publications

(27 citation statements)

References 54 publications

(109 reference statements)

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“…On the other hand, it was reported that fusion pore opening and expansion in neuronal SNARE mediated membrane fusion required specific lipid molecules like cholesterol and acidic lipid PIP 2 (Cho et al, 2007; Lewis et al, 2014; Shin et al, 2010). This could be caused by certain protein regulators, such as C2AB which could significantly change membrane curvature upon binding to specific lipid molecules (Hui et al, 2009; Martens et al, 2007).…”

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confidence: 99%

Lipid molecules influence early stages of yeast SNARE-mediated membrane fusion

Lai

Zhang

et al. 2015

Phys. Biol.

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Lipid molecules, structural components of biomembranes, have been proposed for an important role in membrane fusion. Through various techniques based on protein-reconstituted vesicle-vesicle fusion system, we investigated the influence of several lipid molecules on different stages of yeast SNARE mediated membrane fusion process. Lipid compositions played a significant role in early stages, docking and lipid mixing, while only exhibited a minor effect on fusion pore formation and dilation phases indicated by both small and large content mixing.

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confidence: 99%

Lipid molecules influence early stages of yeast SNARE-mediated membrane fusion

Lai

Zhang

et al. 2015

Phys. Biol.

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“…In 2004, the neuronal porosome complex was first discovered by our group, isolated and functionally reconstituted into artificial lipid membrane using the EPC9 bilayer set‐up . In 2012, the proteome of the neuronal porosome complex , and in 2014, its lipidome was finally determined . Examination of the presynaptic membrane at the nerve terminal using high‐resolution AFM , EM and SAXS studies demonstrate the presence of approximately 15 nm cup‐shaped porosomes, each possessing a central plug (Figs ).…”

Section: Discovery Of the ‘Porosome’mentioning

confidence: 99%

“…Results from this study provide critical insights into the aetiology of CF disease and for potential therapies. Similarly, recent studies using mass spectrometry provide some understanding of the lipidome of the neuronal porosome complex , and the role of Hsp90 in porosome assembly and function , enabling further understanding of the porosome structure–function . Currently, for further understand porosome structure–function, the major focus of our laboratory is to determine the distribution and interaction of proteins and lipids within the porosome complex using chemical crosslinking followed by mass spectrometry, and molecular modelling.…”

Section: Discovery Of the ‘Porosome’mentioning

confidence: 99%

‘Porosome’ discovered nearly 20 years ago provides molecular insights into the kiss‐and‐run mechanism of cell secretion

Jena

2015

J Cellular Molecular Medi

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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.

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“…9 Since calcium is required for SNARE-induced membrane fusion and a loss in porosome-associated interaction between SNAREs and calcium channels is observed following depletion of membrane cholesterol, it is suggested that a loss of cholesterol from the porosome complex would result in the compromise and even possibly abrogation of neurotransmitter release at the nerve terminal. To further understand the role of lipids on porosome structure-function, the lipid composition of isolated neuronal porosome has been determined using mass spectrometry 14 (Tables 3 and 4). Using lipid-binding assays, 14 the affinity of porosome-associated proteins such as syntaxin-1A to various lipids has been determined.…”

Section: Chemistry Of the Porosome Complex In Neuronsmentioning

confidence: 99%

“…Using AFM, 100-180 nm in size secretory portals were observed at the plasma membrane of live pancreatic acinar cells 4 that secreted digestive enzymes through them. The presence and morphology of these secretory portals were further confirmed using electron microscopy (EM), 6,7 and their presence was established in all secretory cells examined including neurons, [7][8][9][10][11][12][13][14][15][16][17][18][19][20] initially by our group [7][8][9][10][11][12][13][14][15][16][17][18][19][20] and subsequently by other laboratories. [21][22][23][24][25][26][27][28][29][30] The function of the porosome as a universal secretory portal, its chemical composition, [7][8][9]13,19,20 and its functional and structural reconstitution,…”

Section: Introductionmentioning

confidence: 95%

The neuronal porosome complex in health and disease

Naik

Lewis

Jena

2015

Exp Biol Med (Maywood)

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Cup-shaped secretory portals at the cell plasma membrane called porosomes mediate the precision release of intravesicular material from cells. Membrane-bound secretory vesicles transiently dock and fuse at the base of porosomes facing the cytosol to expel pressurized intravesicular contents from the cell during secretion. The structure, isolation, composition, and functional reconstitution of the neuronal porosome complex have greatly progressed, providing a molecular understanding of its function in health and disease. Neuronal porosomes are 15 nm cup-shaped lipoprotein structures composed of nearly 40 proteins, compared to the 120 nm nuclear pore complex composed of >500 protein molecules. Membrane proteins compose the porosome complex, making it practically impossible to solve its atomic structure. However, atomic force microscopy and small-angle X-ray solution scattering studies have provided three-dimensional structural details of the native neuronal porosome at sub-nanometer resolution, providing insights into the molecular mechanism of its function. The participation of several porosome proteins previously implicated in neurotransmission and neurological disorders, further attest to the crosstalk between porosome proteins and their coordinated involvement in release of neurotransmitter at the synapse.

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Neuronal porosome lipidome

Cited by 15 publications

References 54 publications

Lipid molecules influence early stages of yeast SNARE-mediated membrane fusion

Lipid molecules influence early stages of yeast SNARE-mediated membrane fusion

‘Porosome’ discovered nearly 20 years ago provides molecular insights into the kiss‐and‐run mechanism of cell secretion

The neuronal porosome complex in health and disease

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