Ca2+ sensor synaptotagmin-1 mediates exocytosis in mammalian photoreceptors

Grassmeyer, Justin J; Cahill, Asia L.; Hays, Cassandra L.; Barta, Cody L.; Quadros, Rolen M.; Gurumurthy, Channabasavaiah B.; Thoreson, Wallace B.

doi:10.7554/elife.45946

Cited by 27 publications

(39 citation statements)

References 127 publications

(174 reference statements)

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“…We affirm the presence of an HCN or i h current activated by hyperpolarization and permeable to both Na + and K + , consistent with the expression of the HCN channels by photoreceptors (Moosmang et al, 2001;Müller et al, 2003). Additionally, our measurements of i Ca are comparable to those recently made by Grassmeyer et al (2019) in both amplitude and voltage dependence. The calcium-activated and voltage-gated conductances we have recorded also have similar properties to those investigated previously (Barnes and Hille, 1989;Xu and Slaughter, 2005;Pelucchi et al, 2008;Stöhr et al, 2009), including in primates (Verweij et al, 2003; but see Yagi and Macleish, 1994).…”

Section: Comparison To Previous Resultssupporting

confidence: 90%

“…EAATs have been proposed to remove glutamate from the photoreceptor synaptic cleft and to have a critical role in the transmission of the photoresponse (Szmajda and Devries, 2011;Tse et al, 2014). Photoreceptors have been reported to express EAATs (Reye et al, 2002;Hasegawa et al, 2006), which can activate to increase membrane permeability to anions and produce a large change in current during glutamate reuptake from the synaptic cleft (see for example Grassmeyer et al, 2019). We think it unlikely that an EAAT current could have contributed to our measurements of reversal potential in Fig.…”

Section: Contribution Of Electrogenic Transportersmentioning

confidence: 92%

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Membrane conductances of mouse cone photoreceptors

Ingram

Sampath

Fain

2020

Journal of General Physiology

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Vertebrate photoreceptor cells respond to light through a closure of CNG channels located in the outer segment. Multiple voltage-sensitive channels in the photoreceptor inner segment serve to transform and transmit the light-induced outer-segment current response. Despite extensive studies in lower vertebrates, we do not know how these channels produce the photoresponse of mammalian photoreceptors. Here we examined these ionic conductances recorded from single mouse cones in unlabeled, dark-adapted retinal slices. First, we show measurements of the voltage dependence of the light response. After block of voltage-gated Ca2+ channels, the light-dependent current was nearly linear within the physiological range of voltages with constant chord conductance and a reversal potential similar to that previously determined in lower vertebrate photoreceptors. At a dark resting membrane potential of −45 mV, cones maintain a standing Ca2+ current (iCa) between 15 and 20 pA. We characterized the time and voltage dependence of iCa and a calcium-activated anion channel. After constitutive closure of the CNG channels by the nonhydrolysable analogue GTP-γ-S, we observed a light-dependent increase in iCa followed by a Ca2+-activated K+ current, both probably the result of feedback from horizontal cells. We also recorded the hyperpolarization-activated cyclic nucleotide-gated (HCN) conductance (ih) and measured its current-voltage relationship and reversal potential. With small hyperpolarizations, ih activated with a time constant of 25 ms; activation was speeded with larger hyperpolarizations. Finally, we characterized two voltage-gated K+-conductances (iK). Depolarizing steps beginning at −10 mV activated a transient, outwardly rectifying iK blocked by 4-AP and insensitive to TEA. A sustained iK isolated through subtraction was blocked by TEA but was insensitive to 4-AP. The sustained iK had a nearly linear voltage dependence throughout the physiological voltage range of the cone. Together these data constitute the first comprehensive study of the channel conductances of mouse photoreceptors.

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Section: Comparison To Previous Resultssupporting

confidence: 90%

Section: Contribution Of Electrogenic Transportersmentioning

confidence: 92%

Membrane conductances of mouse cone photoreceptors

Ingram

Sampath

Fain

2020

Journal of General Physiology

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“…The expression of syt1a in the OPL is consistent with the immunofluorescence data in rat and with the finding that synaptic release from photoreceptors in the mouse is largely controlled by synaptotagmin 1 (Grassmeyer et al, 2019). Additionally, the strong syt1a signal detected in the inner half of the INL and in the GCL is very similar to the one for syt1 mRNA in the mouse (Fox & Sanes, 2007).…”

Section: Synaptotagmins Expressed In the Zebrafish Retinasupporting

confidence: 87%

“…Although synaptotagmin 1 Fox & Sanes, 2007;Grassmeyer et al, 2019), synaptotagmin 2 Fox & Sanes, 2007;Neumann & Haverkamp, 2013), synaptotagmin (Butz et al, 1999;Berntson & Morgans, 2003) and synaptotagmin 7 (Luo et al, 2015) have been found in the retina, only synaptotagmin 1 (Grassmeyer et al, 2019) and synaptotagmin 7 (Luo et al, 2015) were reported to modulate different aspects of release in retinal ribbon-containing neurons. Furthermore, synaptotagmin 1 is thought to underlie alone both modes of synaptic transmission in mammalian cone but not rod photoreceptors (Grassmeyer et al, 2019). To date, the synaptotagmins controlling transient and sustained release in bipolar cells are unknown.…”

Section: Introductionmentioning

confidence: 99%

Expression and distribution of synaptotagmin isoforms in the zebrafish retina

Henry

Joselevitch

Matthews

et al. 2020

Preprint

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Synaptotagmins belong to a large family of proteins. While various synaptotagmins have been implicated as Ca2+ sensors for vesicle replenishment and release at conventional synapses, their roles at retinal ribbon synapses remain incompletely understood. Zebrafish is a widely used experimental model for retinal research. We therefore investigated the homology between human, rat, mouse, and zebrafish synaptotagmins 1 to 10 using a bioinformatics approach. We also characterized the expression and distribution of various synaptotagmin (syt) genes in the zebrafish retina using RT-PCR and in situ hybridization, focusing on the family members whose products likely underlie Ca2+-dependent exocytosis in the central nervous system (synaptotagmins 1, 2, 5 and 7). We find that most zebrafish synaptotagmins are well conserved and can be grouped in the same classes as mammalian synaptotagmins, based on crucial amino acid residues needed for coordinating Ca2+ binding and determining phospholipid binding affinity. The only exception is synaptotagmin 1b, which lacks 34 amino acid residues in the C2B domain and is therefore unlikely to bind Ca2+ there. Additionally, the products of zebrafish syt5a and syt5b genes share identity with mammalian class 1 and 5 synaptotagmins. Zebrafish syt1, syt2, syt5 and syt7 paralogues are found in the zebrafish brain, eye, and retina, excepting syt1b, which is only present in the brain. The complementary expression pattern of the remaining paralogues in the retina suggests that syt1a and syt5a may underlie synchronous release and syt7a and syt7b may mediate asynchronous release or other Ca2+ dependent processes in different types of retinal neurons.

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“…Rod spherules do demark as U-shaped complexes (e.g., in ribeye 30 or PSD95 31 immunostaining); yet, these usually have their base toward the outer nuclear layer (ONL), which is inverse to what we observed for Kcne2. Horizontal cell neurites are predominantly found in the inner part of the OPL, 31 which is also distinct from where we observed Kcne2 immunoreactivity. With this and the RNA-sequencing results in mind, we think that the none-cone portion of the OPL Kcne2 immunoreactivity indeed arises from rod-BCs.…”

Section: Discussionsupporting

confidence: 60%

Expression and Localization ofKcne2in the Vertebrate Retina

Lindner

Gilhooley

Palumaa

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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To characterize the retinal expression and localization of Kcne2, an ancillary (β) ion-channel subunit with an important role in fine-tuning cellular excitability. METHODS. We analyzed available single-cell transcriptome data from tens of thousands of murine retinal cells for cell-type-specific expression of Kcne2 using state-of-the-art bioinformatics techniques. This evidence at the transcriptome level was complemented with a comprehensive immunohistochemical characterization of mouse retina (C57BL/6, ages 8-12 weeks) employing co-labeling techniques and cell-type-specific antibody markers. We furthermore examined how conserved the Kcne2 localization pattern in the retina was across species by performing immunostaining on zebrafish, cowbird, sheep, mice, and macaque. RESULTS. Kcne2 is distinctly expressed in cone photoreceptors and rod bipolar cells. At a subcellular level, the bulk of Kcne2 immunoreactivity can be observed in the outer plexiform layer. Here, it localizes into cone pedicles and likely the postsynaptic membrane of the rod bipolar cells. Thus, the vast majority of Kcne2 immunoreactivity is observed in a thin band in the outer plexiform layer. In addition to this, faint Kcne2 immunoreactivity can also be observed in cone inner segments and the somata of a small subset of cone ON bipolar cells. Strikingly, the localization of Kcne2 in the outer plexiform layer was preserved among all of the species studied, spanning at least 300 million years of evolution of the vertebrate kingdom. CONCLUSIONS. The data we present here suggest an important and specific role for Kcne2 in the highly specialized photoreceptor-bipolar cell synapse.

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Ca2+ sensor synaptotagmin-1 mediates exocytosis in mammalian photoreceptors

Cited by 27 publications

References 127 publications

Membrane conductances of mouse cone photoreceptors

Membrane conductances of mouse cone photoreceptors

Expression and distribution of synaptotagmin isoforms in the zebrafish retina

Expression and Localization ofKcne2in the Vertebrate Retina

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