Oligomeric State of Purified Transient Receptor Potential Melastatin-1 (TRPM1), a Protein Essential for Dim Light Vision

Agosto, Melina A.; Zhang, Zhixian; He, Feng; Anastassov, Ivan; Wright, Sara J.; McGehee, Jennifer; Wensel, Theodore G.

doi:10.1074/jbc.m114.593780

Cited by 20 publications

(25 citation statements)

References 80 publications

(78 reference statements)

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“…This requirement for an associated protein has also been proposed in two other studies. In the first, it was suggested because TRPM1 was shown to lack 4-fold symmetry 43 , characteristic of channel oligomerization seen for TRPV1 and other TRP channels, and in the second becasue capsaisin could not stimulate heterogeneously expressed TRPM1 44 . One possibility is that Gα o is this auxiliary protein, and four lines of evidence support this idea.…”

Section: Discussionmentioning

confidence: 99%

The TRPM1 channel in ON-bipolar cells is gated by both the α and the βγ subunits of the G-protein Go

Orlandi

Cao

et al. 2016

Sci Rep

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Transmission from photoreceptors to ON bipolar cells in mammalian retina is mediated by a sign-inverting cascade. Upon binding glutamate, the metabotropic glutamate receptor mGluR6 activates the heterotrimeric G-protein Gαoβ3γ13, and this leads to closure of the TRPM1 channel (melastatin). TRPM1 is thought to be constitutively open, but the mechanism that leads to its closure is unclear. We investigated this question in mouse rod bipolar cells by dialyzing reagents that modify the activity of either Gαo or Gβγ and then observing their effects on the basal holding current. After opening the TRPM1 channels with light, a constitutively active mutant of Gαo closed the channel, but wild-type Gαo did not. After closing the channels by dark adaptation, phosducin or inactive Gαo (both sequester Gβγ) opened the channel while the active mutant of Gαo did not. Co-immunoprecipitation showed that TRPM1 interacts with Gβ3 and with the active and inactive forms of Gαo. Furthermore, bioluminescent energy transfer assays indicated that while Gαo interacts with both the N- and the C- termini of TRPM1, Gβγ interacts only with the N-terminus. Our physiological and biochemical results suggest that both Gαo and Gβγ bind TRPM1 channels and cooperate to close them.

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Section: Discussionmentioning

confidence: 99%

The TRPM1 channel in ON-bipolar cells is gated by both the α and the βγ subunits of the G-protein Go

Orlandi

Cao

et al. 2016

Sci Rep

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“…The following antibodies and reagents were used for immunostaining: rabbit anti-Cre (#69050), and mouse anti-ubiquitin (#04-263) were from EMD Millipore; rabbit anti-GRP78/BiP (#PA1-014A), rabbit anti-TGN46 (#PA5-23068), Armenian hamster anti-Atg9 (#MA1-149), rabbit anti-ZO-1/TJP1 (#402200) and Alexa Fluor 647 phalloidin (#A22287) were from Thermo Fisher; mouse anti-GM130 was from BD Biosciences (#610822); rabbit anti-Rab5 (#3547, C8B1), rabbit anti-Rab7 (#9367, D95F2), rabbit anti-LC3A/B (#12741) and rabbit anti-EEA1 (#3288S, C45B10) were from Cell Signaling; mouse anti-LC3 (#AM1800a) was from Abgent; guinea pig anti-p62 (#03-GP62-C) was from American Research Products; purified monoclonal 1D4 (Molday & MacKenzie, 1983) was prepared in-house from hybridoma culture medium as described (Agosto et al, 2014); mouse anti-LAMP2 (#ab25631), rabbit anti-Rab11a (#ab128913), rabbit anti-Atg9 (#PA1-16993) and mouse anti-RPE65 (#MA1-16578) were from Abcam; mouse anti-LAMP1 (##428017) was from Calbiochem; mouse anti-Atg16L (#M150) and rabbit anti-Atg16L (#PM040) were from MBL. Donkey secondary antibodies conjugated with Alexa dyes (#A21206, #A21206, #A31572, # A21202, #A31571 and #A32773) were from Thermo.…”

Section: Immunofluorescence Stainingmentioning

confidence: 99%

Multiple phosphatidylinositol(3)phosphate roles in retinal pigment epithelium membrane recycling

et al. 2020

Preprint

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The low-abundance lipid phosphatidylinositol-3-phosphate (PI(3)P) is important for membrane dynamics in autophagy, endosome processing, and phagocytosis. In retinal pigmented epithelial cells (RPE) all three pathways are important, but phagocytosis of disk membranes shed from adjacent photoreceptors is especially important for ensuring health of photoreceptors and preventing retinal degeneration. By eliminating Vps34, the kinase responsible for synthesizing PI(3)P in RPE, we have found that PI(3)P plays distinct roles in each pathway. In phagocytosis it is not required for disk engulfment or phagosome transport but is essential for recruitment and lipidation of LC3. In contrast, initiation of autophagy and LC3 recruitment to autophagosomes does not require PI(3)P, which can be bypassed by an alternative mechanism of ATG16L recruitment that does not require PI(3)P, Rab11a, or WIPI2. In all three pathways, PI(3)P is essential for fusion with lysosomes; autophagosomes, phagosomes, and Rab7-positive late endosomes, as well as enlarged lysosomes, accumulate in large numbers in the absence of Vps34, leading to cell death.

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“…The glutamate receptor, mGluR6, signals via the heterotrimeric G protein G o , which in turn gates a transduction channel by an unknown mechanism (for review, see Martemyanov and Sampath, 2017 ). Transient receptor potential melastatin-1 (TRPM1) is required for channel function ( Audo et al, 2009 ; Li et al, 2009 ; Morgans et al, 2009 ; Shen et al, 2009 ; Van Genderen et al, 2009 ; Koike et al, 2010b ), but it is not known if it is sufficient for formation of the G o -sensitive channel ( Lambert et al, 2011 ; Agosto et al, 2014 ; Schneider et al, 2015 ; Martemyanov and Sampath, 2017 ). In the dark, tonic release of glutamate activates mGluR6, keeping the channel closed; at light onset, decrease in glutamate release and deactivation of mGluR6 lead to channel opening and membrane depolarization.…”

Section: Introductionmentioning

confidence: 99%

A Large Endoplasmic Reticulum-Resident Pool of TRPM1 in Retinal ON-Bipolar Cells

Agosto

Anastassov

Robichaux

et al. 2018

eNeuro

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The chemical signal of light onset, a decrease in glutamate release from rod and cone photoreceptors, is processed by a postsynaptic G protein signaling cascade in ON-bipolar cells (BPCs). The metabotropic glutamate receptor mGluR6, along with other cascade elements, is localized synaptically at the BPC dendritic tips. The effector ion channel protein transient receptor potential melastatin-1 (TRPM1), in contrast, is located not only at the dendritic tips but also in BPC bodies and axons. Little is known about the intracellular localization of TRPM1, or its trafficking route to the dendritic tip plasma membrane. Recombinant TRPM1 expressed in mammalian cells colocalized with endoplasmic reticulum (ER) markers, with little or none detected at the plasma membrane. In mouse retina, somatic TRPM1 was similarly intracellular, and not at the plasma membrane. Labeling of ER membranes by expression of a fluorescent marker showed that in BPCs the ER extends into axons and dendrites, but not dendritic tips. In cell bodies, TRPM1 colocalized with the ER, and not with the Golgi apparatus. Fluorescence protease protection (FPP) assays with TRPM1-GFP fusions in heterologous cells revealed that the N and C termini are both accessible to the cytoplasm, consistent with the transmembrane domain topology of related TRP channels. These results indicate that the majority of TRPM1 is present in the ER, from which it can potentially be transported to the dendritic tips as needed for ON light responses. The excess of ER-resident TRPM1 relative to the amount needed at the dendritic tips suggests a potential new function for TRPM1 in the ER.

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Oligomeric State of Purified Transient Receptor Potential Melastatin-1 (TRPM1), a Protein Essential for Dim Light Vision

Cited by 20 publications

References 80 publications

The TRPM1 channel in ON-bipolar cells is gated by both the α and the βγ subunits of the G-protein Go

The TRPM1 channel in ON-bipolar cells is gated by both the α and the βγ subunits of the G-protein Go

Multiple phosphatidylinositol(3)phosphate roles in retinal pigment epithelium membrane recycling

A Large Endoplasmic Reticulum-Resident Pool of TRPM1 in Retinal ON-Bipolar Cells

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