Clint Makino - Academia.edu (original) (raw)

Papers by Clint Makino

The Journal of General Physiology, Jul 1, 1996

Brain Research, May 1, 1984

Neurobiology of Aging, Sep 1, 1981

... 49: 453466, 1958. 23. Howe, GR, JD Butch, AB Miller, B. Morrison, P. Gor don, L. Weldon, LW C... more ... 49: 453466, 1958. 23. Howe, GR, JD Butch, AB Miller, B. Morrison, P. Gor don, L. Weldon, LW Chambers, G. Fodor and GM Winsor. Artificial sweeteners and human bladder cancer. Lancet 2: 578581, 1977. 24. Kier. LB A molecular theory of sweet taste. J. Pharm. Sci. ...

Visual Neuroscience, Nov 1, 2011

Frontiers in Molecular Neuroscience, Mar 6, 2015

The Journal of General Physiology, Dec 1, 1990

Exposure of an intact vertebrate eye to light bleaches the rhodopsin in the photoreceptor outer s... more Exposure of an intact vertebrate eye to light bleaches the rhodopsin in the photoreceptor outer segments in spatially nonuniform patterns. Some axial bleaching patterns produced in toad rods were determined using microspectrophotometric techniques. More rhodopsin was bleached at the base of the outer segment than at the distal tip. The shape of the bleaching gradient varied with the extent of bleach and with the spectral content of the illuminant. Monochromatic light at the lambda max of the rhodopsin gave rise to the steepest bleaching gradients and induced the greatest changes in the form of the gradient with increasing extent of bleach. These results were consistent with a mathematical model for pigment bleaching in an unstirred sample. The model did not fit bleaching patterns resulting from special lighting conditions that promoted the photoregeneration of rhodopsin from the intermediates of bleaching. Prolonged light adaptation of toads could also produce axial rhodopsin gradients that were not fit by the bleaching model. Under certain conditions the axial gradient of rhodopsin in a rod outer segment reversed with time in the light: the rhodopsin content became highest at the base. This result could be explained by an interaction between the pattern of bleaching and the intracellular topography of regeneration.

Current Opinion in Neurobiology, Aug 1, 2003

Transgenic mice bearing null or functional mutations are being used to define the roles of specif... more Transgenic mice bearing null or functional mutations are being used to define the roles of specific elements in phototransduction and also to time the molecular interactions. Genetic manipulation of the collision frequency between rhodopsin and transducin molecules identified this parameter as rate-limiting for the photoresponse onset. Genetic interference with rhodopsin phosphorylation and arrestin binding, transducin shut-off and calcium feedback has revealed their respective roles in shaping the response waveform. The timetable for all of these molecular events determines the amplitude, kinetics and reproducibility of the photoresponse.

Science, Jan 20, 1995

saturation. After resuspension and dialysis [20 mM tris-HCI (pH 7.5)], the proteins were separate... more saturation. After resuspension and dialysis [20 mM tris-HCI (pH 7.5)], the proteins were separated by IEF in the pH range 4 to 6.5 with the RF3 Protein Fractionator (Texas Instruments). Active fractions were pooled, desalted, and exchanged into 20 mM sodium phosphate buffer (pH 7.0) with 0.2 M sodium chloride with the use of Centricon C-30 spin columns (Amicom, Beverly, MA). Gel filtration was done on a 7.8 x 250 mm TSK G3000 SW XL HPLC column (Tosoh Corporation, Japan) in the same buffer. Active fractions were pooled and then fractionated by SDS-polyacrylamide gel electrophoresis. The band corresponding to avenacinase (10) was electroeluted and used to immunize Wistar rats. The resulting polyclonal antiserum was used for protein immunoblot analysis and cDNA library screening at a dilution of 1:2000. Control experiments with preimmune serum (diluted 1 100) gave no signal. Rabbit antibody to rat immunoglobulin G alkaline phosphatase conjugate was used as the secondary antibody. A Gga cDNA expression library was constructed in lambda gt 1 by standard methods [

PLOS ONE, Oct 14, 2020

Retinal rods function as accurate photon counters to provide for vision under very dim light. To ... more Retinal rods function as accurate photon counters to provide for vision under very dim light. To do so, rods must generate highly amplified, reproducible responses to single photons, yet outer segment architecture and randomness in the location of rhodopsin photoisomerization on the surface of an internal disk introduce variability to the rising phase of the photon response. Soon after a photoisomerization at a disk rim, depletion of cGMP near the plasma membrane closes ion channels and hyperpolarizes the rod. But with a photoisomerization in the center of a disk, local depletion of cGMP is distant from the channels in the plasma membrane. Thus, channel closure is delayed by the time required for the reduction of cGMP concentration to reach the plasma membrane. Moreover, the local fall in cGMP dissipates over a larger volume before affecting the channels, so response amplitude is reduced. This source of variability increases with disk radius. Using a fully space-resolved biophysical model of rod phototransduction, we quantified the variability attributable to randomness in the location of photoisomerization as a function of disk structure. In mouse rods that have small disks bearing a single incisure, this variability was negligible in the absence of the incisure. Variability was increased slightly by the incisure, but randomness in the shutoff of rhodopsin emerged as the main source of single photon response variability at all but the earliest times. Variability arising from randomness in the transverse location of photoisomerization increased in magnitude and persisted over a longer period in the photon response of large salamander rods. A symmetric arrangement of multiple incisures in the disks of salamander rods greatly reduced this variability during the rising phase, but the incisures had the opposite effect on variability arising from randomness in rhodopsin shutoff at later times.

Investigative Ophthalmology & Visual Science, May 1, 2005

Frontiers in Molecular Neuroscience, Apr 14, 2023

Rod photoreceptors in the retina adjust their responsiveness and sensitivity so that they can con... more Rod photoreceptors in the retina adjust their responsiveness and sensitivity so that they can continue to provide meaningful information over a wide range of light intensities. By stimulating membrane guanylate cyclases in the outer segment to synthesize cGMP at a faster rate in a Ca 2+-dependent fashion, bicarbonate increases the circulating "dark" current and accelerates flash response kinetics in amphibian rods. Compared to amphibian rods, mammalian rods are smaller in size, operate at a higher temperature, and express visual cascade proteins with somewhat different biochemical properties. Here, we evaluated the role of bicarbonate in rods of cpfl3 mice. These mice are deficient in their expression of functional cone transducin, Gnat2, making cones very insensitive to light, so the rod response to light could be observed in isolation in electroretinogram recordings. Bicarbonate increased the dark current and absolute sensitivity and quickened flash response recovery in mouse rods to a greater extent than in amphibian rods. In addition, bicarbonate enabled mouse rods to respond over a range that extended to dimmer flashes. Larger flash responses may have resulted in part from a bicarbonate-induced elevation in intracellular pH. However, high pH alone had little effect on flash response recovery kinetics and even suppressed the accelerating effect of bicarbonate, consistent with a direct, modulatory action of bicarbonate on Ca 2+-dependent, membrane guanylate cyclase activity.

The Journal of Neuroscience, 1995

The Journal of Physiology, May 31, 2012

Visual Neuroscience, May 1, 2009

Vision begins with photoisomerization of 11-cis retinal to the all-trans conformation within the ... more Vision begins with photoisomerization of 11-cis retinal to the all-trans conformation within the chromophore-binding pocket of opsin, leading to activation of a biochemical cascade. Release of all-trans retinal from the binding pocket curtails but does not fully quench the ability of opsin to activate transducin. All-trans retinal and some other analogs, such as β-ionone, enhance opsin's activity, presumably on binding the empty chromophore-binding pocket. By recording from isolated salamander photoreceptors and from patches of rod outer segment membrane, we now show that high concentrations of β-ionone suppressed circulating current in dark-adapted greensensitive rods by inhibiting the cyclic nucleotide-gated channels. There were also decreases in circulating current and flash sensitivity, and accelerated flash response kinetics in dark-adapted blue-sensitive (BS) rods and cones, and in ultraviolet-sensitive cones, at concentrations too low to inhibit the channels. These effects persisted in BS rods even after incubation with 9-cis retinal to ensure complete regeneration of their visual pigment. After long exposures to high concentrations of β-ionone, recovery was incomplete unless 9-cis retinal was given, indicating that visual pigment had been bleached. Therefore, we propose that β-ionone activates and bleaches some types of visual pigments, mimicking the effects of light.

Frontiers in Molecular Neuroscience, Jan 28, 2016

Photoreceptor ROS-GC1, a prototype subfamily member of the membrane guanylate cyclase family, is ... more Photoreceptor ROS-GC1, a prototype subfamily member of the membrane guanylate cyclase family, is a central component of phototransduction. It is a single transmembrane-spanning protein, composed of modular blocks. In rods, guanylate cyclase activating proteins (GCAPs) 1 and 2 bind to its juxtamembrane domain (JMD) and the C-terminal extension, respectively, to accelerate cyclic GMP synthesis when Ca 2+ levels are low. In cones, the additional expression of the Ca 2+-dependent guanylate cyclase activating protein (CD-GCAP) S100B which binds to its C-terminal extension, supports acceleration of cyclic GMP synthesis at high Ca 2+ levels. Independent of Ca 2+ , ROS-GC1 activity is also stimulated directly by bicarbonate binding to the core catalytic domain (CCD). Several enticing molecular features of this transduction system are revealed in the present study. In combination, bicarbonate and Ca 2+-dependent modulators raised maximal ROS-GC activity to levels that exceeded the sum of their individual effects. The F 514 S mutation in ROS-GC1 that causes blindness in type 1 Leber's congenital amaurosis (LCA) severely reduced basal ROS-GC1 activity. GCAP2 and S100B Ca 2+ signaling modes remained functional, while the GCAP1-modulated mode was diminished. Bicarbonate nearly restored basal activity as well as GCAP2-and S100B-stimulated activities of the F 514 S mutant to normal levels but could not resurrect GCAP1 stimulation. We conclude that GCAP1 and GCAP2 forge distinct pathways through domain-specific modules of ROS-GC1 whereas the S100B and GCAP2 pathways may overlap. The synergistic interlinking of bicarbonate to GCAPs-and S100B-modulated pathways intensifies and tunes the dependence of cyclic GMP synthesis on intracellular Ca 2+. Our study challenges the recently proposed GCAP1 and GCAP2 "overlapping" phototransduction model (Peshenko et al., 2015b).

Investigative Ophthalmology & Visual Science, Jun 21, 2021

Investigative Ophthalmology & Visual Science, 2003