Full Text Journal Articles by
Author Ronald W Holz

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Roles for the SNAP25 linker domain in the fusion pore and a dynamic plasma membrane SNARE "acceptor" complex.

Ronald W Holz, Mary A Bittner,

Central to the exocytotic release of hormones and neurotransmitters is the interaction of four SNARE motifs in proteins on the secretory granule/synaptic vesicle membrane (synaptobrevin/VAMP, v-SNARE) and on the plasma membrane (syntaxin and SNAP25, t-SNAREs). The interaction is thought to bring the opposing membranes together to enable fusion. An underlying ... Read more >>

J Gen Physiol (The Journal of general physiology)
[2020, 152(9):]

Cited: 0 times

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Dynamic Relationship of the SNARE Complex with a Membrane.

Ronald W Holz, Joshua Zimmerberg,

Fusion of secretory granules and synaptic vesicles with the plasma membrane is driven by SNARE protein interactions. Intensive investigations in vitro, which include x-ray crystallography, cryoelectron microscopy, and NMR analyses by numerous groups, have elucidated structures relevant to the function of these proteins. Although function depends on the proteins being membrane ... Read more >>

Biophys J (Biophysical journal)
[2019, 117(4):627-630]

Cited: 4 times

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Visualization of expanding fusion pores in secretory cells.

Prabhodh S Abbineni, Daniel Axelrod, Ronald W Holz,

J Gen Physiol (The Journal of general physiology)
[2018, 150(12):1640-1646]

Cited: 4 times

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Identification of β-synuclein on secretory granules in chromaffin cells and the effects of α- and β-synuclein on post-fusion BDNF discharge and fusion pore expansion.

Prabhodh S Abbineni, Kevin P Bohannon, Mary A Bittner, Daniel Axelrod, Ronald W Holz,

α-Synuclein is strongly implicated in the pathogenesis of Parkinson's disease as well as in other neurodegenerative diseases. However, its normal function in cells is not understood. The N-termini of α-, β-, and γ-synuclein contains six to seven 11-amino acid repeats that are predicted to form amphipathic helices. Membrane-binding and membrane-curving ... Read more >>

Neurosci Lett (Neuroscience letters)
[2019, 699:134-139]

Cited: 2 times

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Chromogranin A, the major lumenal protein in chromaffin granules, controls fusion pore expansion.

Prabhodh S Abbineni, Mary A Bittner, Daniel Axelrod, Ronald W Holz,

Upon fusion of the secretory granule with the plasma membrane, small molecules are discharged through the immediately formed narrow fusion pore, but protein discharge awaits pore expansion. Recently, fusion pore expansion was found to be regulated by tissue plasminogen activator (tPA), a protein present within the lumen of chromaffin granules ... Read more >>

J Gen Physiol (The Journal of general physiology)
[2019, 151(2):118-130]

Cited: 4 times

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Refractive Index Imaging of Cells with Variable-Angle Near-Total Internal Reflection (TIR) Microscopy.

Kevin P Bohannon, Ronald W Holz, Daniel Axelrod,

The refractive index in the interior of single cells affects the evanescent field depth in quantitative studies using total internal reflection (TIR) fluorescence, but often that index is not well known. We here present method to measure and spatially map the absolute index of refraction in a microscopic sample, by ... Read more >>

Microsc Microanal (Microscopy and microanalysis : the official journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada)
[2017, 23(5):978-988]

Cited: 4 times

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Slow fusion pore expansion creates a unique reaction chamber for co-packaged cargo.

Kevin P Bohannon, Mary A Bittner, Daniel A Lawrence, Daniel Axelrod, Ronald W Holz,

A lumenal secretory granule protein, tissue plasminogen activator (tPA), greatly slows fusion pore dilation and thereby slows its own discharge. We investigated another outcome of the long-lived narrow fusion pore: the creation of a nanoscale chemical reaction chamber for granule contents in which the pH is suddenly neutralized upon fusion. ... Read more >>

J Gen Physiol (The Journal of general physiology)
[2017, 149(10):921-934]

Cited: 9 times

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Food deprivation induces presynaptic plasticity in the autonomic nervous system.

Ronald W Holz, Arun Anantharam,

Proc Natl Acad Sci U S A (Proceedings of the National Academy of Sciences of the United States of America)
[2016, 113(21):5766-5767]

Cited: 1 time

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Lumenal protein within secretory granules affects fusion pore expansion.

Annita Ngatchou Weiss, Arun Anantharam, Mary A Bittner, Daniel Axelrod, Ronald W Holz,

It is often assumed that upon fusion of the secretory granule membrane with the plasma membrane, lumenal contents are rapidly discharged and dispersed into the extracellular medium. Although this is the case for low-molecular-weight neurotransmitters and some proteins, there are numerous examples of the dispersal of a protein being delayed ... Read more >>

Biophys J (Biophysical journal)
[2014, 107(1):26-33]

Cited: 17 times

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Protein mobility within secretory granules.

Annita Ngatchou Weiss, Mary A Bittner, Ronald W Holz, Daniel Axelrod,

We investigated the basis for previous observations that fluorescent-labeled neuropeptide Y (NPY) is usually released within 200 ms after fusion, whereas labeled tissue plasminogen activator (tPA) is often discharged over many seconds. We found that tPA and NPY are endogenously expressed in small and different subpopulations of bovine chromaffin cells in ... Read more >>

Biophys J (Biophysical journal)
[2014, 107(1):16-25]

Cited: 7 times

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Cell biology. Dynamin flexibility drives fission.

Ronald W Holz,

Science (Science (New York, N.Y.))
[2013, 339(6126):1392-1393]

Cited: 2 times

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A nibbling mechanism for clathrin-mediated retrieval of secretory granule membrane after exocytosis.

Mary A Bittner, Rachel L Aikman, Ronald W Holz,

Clathrin-mediated endocytosis is the major pathway for recycling of granule membrane components after strong stimulation and high exocytotic rates. It resembles "classical" receptor-mediated endocytosis but has a trigger that is unique to secretion, the sudden appearance of the secretory granule membrane in the plasma membrane. The spatial localization, the relationship ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2013, 288(13):9177-9188]

Cited: 14 times

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Peptide ordering within nuclear pores in living cells.

Ronald W Holz,

Biophys J (Biophysical journal)
[2013, 104(1):6-7]

Cited: 0 times

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Real-time imaging of plasma membrane deformations reveals pre-fusion membrane curvature changes and a role for dynamin in the regulation of fusion pore expansion.

Arun Anantharam, Daniel Axelrod, Ronald W Holz,

Assays for real-time investigation of exocytosis typically measure what is released from the granule. From this, inferences are made about the dynamics of membrane remodeling as fusion progresses from start to finish. We have recently undertaken a different approach to investigate the fusion process, by focusing not primarily on the ... Read more >>

J Neurochem (Journal of neurochemistry)
[2012, 122(4):661-671]

Cited: 21 times

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Subunit-dependent axonal trafficking of distinct alpha heteromeric potassium channel complexes.

Paul M Jenkins, Jeremy C McIntyre, Lian Zhang, Arun Anantharam, Eileen D Vesely, Kristin L Arendt, Cynthia J L Carruthers, Tom K Kerppola, Jorge A Iñiguez-Lluhí, Ronald W Holz, Michael A Sutton, Jeffrey R Martens,

Voltage-gated potassium (Kv) channels are critical for neuronal excitability and are targeted to specific subcellular compartments to carry out their unique functions. While it is widely believed that Kv channels exist as heteromeric complexes in neurons, direct tests of the hypothesis that specific heteromeric channel populations display divergent spatial and ... Read more >>

J Neurosci (The Journal of neuroscience : the official journal of the Society for Neuroscience)
[2011, 31(37):13224-13235]

Cited: 11 times

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A new role for the dynamin GTPase in the regulation of fusion pore expansion.

Arun Anantharam, Mary A Bittner, Rachel L Aikman, Edward L Stuenkel, Sandra L Schmid, Daniel Axelrod, Ronald W Holz,

Dynamin is a master regulator of membrane fission in endocytosis. However, a function for dynamin immediately upon fusion has also been suspected from a variety of experiments that measured release of granule contents. The role of dynamin guanosine triphosphate hydrolase (GTPase) activity in controlling fusion pore expansion and postfusion granule ... Read more >>

Mol Biol Cell (Molecular biology of the cell)
[2011, 22(11):1907-1918]

Cited: 75 times

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Polarized TIRFM reveals changes in plasma membrane topology before and during granule fusion.

Arun Anantharam, Daniel Axelrod, Ronald W Holz,

We have recently developed a combination of polarization and total internal reflection fluorescence microscopy (pTIRFM) to monitor changes in plasma membrane topology occurring after fusion of chromaffin granules. In this report, pTIRFM is further exploited to reveal two major findings in regards to the secretory pathway in bovine chromaffin cells. ... Read more >>

Cell Mol Neurobiol (Cellular and molecular neurobiology)
[2010, 30(8):1343-1349]

Cited: 16 times

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Localized topological changes of the plasma membrane upon exocytosis visualized by polarized TIRFM.

Arun Anantharam, Bibiana Onoa, Robert H Edwards, Ronald W Holz, Daniel Axelrod,

Total internal reflection fluorescence microscopy (TIRFM) images the plasma membrane-cytosol interface and has allowed insights into the behavior of individual secretory granules before and during exocytosis. Much less is known about the dynamics of the other partner in exocytosis, the plasma membrane. In this study, we report the implementation of ... Read more >>

J Cell Biol (The Journal of cell biology)
[2010, 188(3):415-428]

Cited: 59 times

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Misfolded proinsulin affects bystander proinsulin in neonatal diabetes.

Israel Hodish, Ming Liu, Gautam Rajpal, Dennis Larkin, Ronald W Holz, Aaron Adams, Leanza Liu, Peter Arvan,

It has previously been shown that misfolded mutant Akita proinsulin in the endoplasmic reticulum engages directly in protein complexes either with nonmutant proinsulin or with "hProCpepGFP" (human proinsulin bearing emerald-GFP within the C-peptide), impairing the trafficking of these "bystander" proinsulin molecules (Liu, M., Hodish, I., Rhodes, C. J., and Arvan, ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2010, 285(1):685-694]

Cited: 42 times

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Dopamine and amphetamine rapidly increase dopamine transporter trafficking to the surface: live-cell imaging using total internal reflection fluorescence microscopy.

Cheryse A Furman, Rong Chen, Bipasha Guptaroy, Minjia Zhang, Ronald W Holz, Margaret Gnegy,

Rapid treatment (1 min) of rat striatal synaptosomes with low-dose amphetamine increases surface expression of the dopamine transporter (DAT). Using mouse neuroblastoma N2A cells, stably transfected with green fluorescent protein-DAT, we demonstrate the real-time substrate-induced rapid trafficking of DAT to the plasma membrane using total internal reflection fluorescence microscopy (TIRFM). ... Read more >>

J Neurosci (The Journal of neuroscience : the official journal of the Society for Neuroscience)
[2009, 29(10):3328-3336]

Cited: 56 times

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Pharmacology meets vesicular trafficking at a central nervous system synapse: pregabalin effects on synaptic vesicle cycling in hippocampal neurons.

Ronald W Holz,

The contribution by Micheva et al. in this issue of Molecular Pharmacology adds to our understanding of the action of pregabalin, a drug used for treatment of partial seizures and neuropathic pain. The authors examine the effects of pregabalin on presynaptic function of cultured hippocampal neurons using a powerful technique ... Read more >>

Mol Pharmacol (Molecular pharmacology)
[2006, 70(2):444-446]

Cited: 4 times

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Analysis of the late steps of exocytosis: biochemical and total internal reflection fluorescence microscopy (TIRFM) studies.

Ronald W Holz,

1. Time with Julie in his laboratory at the NIH in the early 1970s is remembered. The experience led to a life-long interest in the regulation of catecholamine secretion. Here are summarized aspects of this work. 2. The relationship between ATP-dependent priming of exocytosis and the polyphosphoinositides is reviewed. In ... Read more >>

Cell Mol Neurobiol (Cellular and molecular neurobiology)
[2006, 26(4-6):439-447]

Cited: 4 times

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Phosphatidylinositol-4,5-bisphosphate: actin dynamics and the regulation of ATP-dependent and -independent secretion.

Mary A Bittner, Ronald W Holz,

It has long been believed that the cortical actin cytoskeleton plays an important role in regulating the secretion of hormones and neurotransmitters. In this study, we investigated the control of actin dynamics in primary neuroendocrine cells and determined the relationship of actin dynamics to various components of the secretory response. ... Read more >>

Mol Pharmacol (Molecular pharmacology)
[2005, 67(4):1089-1098]

Cited: 22 times

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Visualization of regulated exocytosis with a granule-membrane probe using total internal reflection microscopy.

Miriam W Allersma, Li Wang, Daniel Axelrod, Ronald W Holz,

Secretory granules labeled with Vamp-green fluorescent protein (GFP) showed distinct signatures upon exocytosis when viewed by total internal reflection fluorescence microscopy. In approximately 90% of fusion events, we observed a large increase in fluorescence intensity coupled with a transition from a small punctate appearance to a larger, spreading cloud with ... Read more >>

Mol Biol Cell (Molecular biology of the cell)
[2004, 15(10):4658-4668]

Cited: 76 times

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Rim, a component of the presynaptic active zone and modulator of exocytosis, binds 14-3-3 through its N terminus.

Lei Sun, Mary A Bittner, Ronald W Holz,

Rim1, a brain-specific Rab3a-binding protein, localizes to the presynaptic cytomatrix and plays an important role in synaptic transmission and synaptic plasticity. Rim2, a homologous protein, is more ubiquitously expressed and is found in neuroendocrine cells as well as in brain. Both Rim1 and Rim2 contain multiple domains, including an N-terminal ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2003, 278(40):38301-38309]

Cited: 39 times

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