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Differential epitope masking reveals synapse-specific complexes of TRPM1

Published online by Cambridge University Press:  26 January 2018

MELINA A. AGOSTO Open the ORCID record for MELINA A. AGOSTO [Opens in a new window] ,
IVAN A. ANASTASSOV  and
THEODORE G. WENSEL
MELINA A. AGOSTO*
Affiliation:
Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030
IVAN A. ANASTASSOV
Affiliation:
Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030
THEODORE G. WENSEL
Affiliation:
Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030
*
*Address correspondence to: Melina A. Agosto, Department of Biochemistry and Molecular Biology, BCM-125, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030. E-mail: [email protected]
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Abstract

The transient receptor potential channel TRPM1 is required for synaptic transmission between photoreceptors and the ON subtype of bipolar cells (ON-BPC), mediating depolarization in response to light. TRPM1 is present in the somas and postsynaptic dendritic tips of ON-BPCs. Monoclonal antibodies generated against full-length TRPM1 were found to have differential labeling patterns when used to immunostain the mouse retina, with some yielding reduced labeling of dendritic tips relative to the labeling of cell bodies. Epitope mapping revealed that those antibodies that poorly label the dendritic tips share a binding site (N2d) in the N-terminal arm near the transmembrane domain. A major splice variant of TRPM1 lacking exon 19 does not contain the N2d binding site, but quantitative immunoblotting revealed no enrichment of this variant in synaptsomes. One explanation of the differential labeling is masking of the N2d epitope by formation of a synapse-specific multiprotein complex. Identifying the binding partners that are specific for the fraction of TRPM1 present at the synapses is an ongoing challenge for understanding TRPM1 function.

Keywords

TRPM1ON bipolar cellEpitope mappingEpitope masking
Type
Research Article
Information
Visual Neuroscience , Volume 35 , 2018 , E001
Copyright
Copyright © Cambridge University Press 2018 

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Footnotes

†

Current address: Department of Ophthalmology, University of California, San Francisco, California 94143

References

Agosto, M.A., Zhang, Z., He, F., Anastassov, I.A., Wright, S.J., McGehee, J. & Wensel, T.G. (2014). Oligomeric state of purified transient receptor potential melastatin-1 (TRPM1), a protein essential for dim light vision. Journal of Biological Chemistry 289, 27019–27033.Google Scholar
Audo, I., Kohl, S., Leroy, B.P., Munier, F.L., Guillonneau, X., Mohand-Saıd, S., Bujakowska, K., Nandrot, E.F., Lorenz, B., Preising, M., Kellner, U., Renner, A.B., Bernd, A., Antonio, A., Moskova-Doumanova, V., Lancelot, M., Poloschek, C.M., Drumare, I., Defoort-Dhellemmes, S., Wissinger, B., Leveillard, T., Hamel, C.P., Schorderet, D.F., De Baere, E., Berger, W., Jacobson, S.G., Zrenner, E., Sahel, J-A., Bhattacharya, S.S. & Zeitz, C. (2009). TRPM1 is mutated in patients with autosomal-recessive complete congenital stationary night blindness. The American Journal of Human Genetics 85, 720–729.CrossRefGoogle ScholarPubMed
Audo, I., Bujakowska, K., Orhan, E., Poloschek, C.M., Defoort-Dhellemmes, S., Drumare, I., Kohl, S., Luu, T.D., Lecompte, O., Zrenner, E., Lancelot, M-E., Antonio, A., Germain, A., Michiels, C., Audier, C., Letexier, M., Saraiva, J-P., Leroy, B.P., Munier, F.L., Mohand-Saïd, S., Lorenz, B., Friedburg, C., Preising, M., Kellner, U., Renner, A.B., Moskova-Doumanova, V., Berger, W., Wissinger, B., Hamel, C.P., Schorderet, D.F., De Baere, E., Sharon, D., Banin, E., Jacobson, S.G., Bonneau, D., Zanlonghi, X., Le Meur, G., Casteels, I., Koenekoop, R., Long, V.W., Meire, F., Prescott, K., de Ravel, T., Simmons, I., Nguyen, H., Dollfus, H., Poch, O., Léveillard, T., Nguyen-Ba-Charvet, K., Sahel, J-A., Bhattacharya, S.S. & Zeitz, C. (2012). Whole-exome sequencing identifies mutations in GPR179 leading to autosomal-recessive complete congenital stationary night blindness. The American Journal of Human Genetics 90, 321–330.Google Scholar
Bech-Hansen, N.T., Naylor, M.J., Maybaum, T.A., Sparkes, R.L., Koop, B., Birch, G., Bergen, A.A.B., Prinsen, C.F.M., Polomeno, R.C., Gal, A., Drack, A.V., Musarella, M.A., Jacobson, S.G., Young, R.S.L. & Weleber, R.G. (2000). Mutations in NYX, encoding the leucine-rich proteoglycan nyctalopin, cause X-linked complete congenital stationary night blindness. Nature Genetics 26, 319–323.Google Scholar
Cao, Y., Pahlberg, J., Sarria, I., Kamasawa, N., Sampath, A.P. & Martemyanov, K.A. (2012). Regulators of G protein signaling RGS7 and RGS11 determine the onset of the light response in ON bipolar neurons. Proceedings of the National Academy of Sciences of the United States of America 109, 7905–7910.Google Scholar
Cao, Y., Posokhova, E. & Martemyanov, K.A. (2011). TRPM1 forms complexes with nyctalopin in vivo and accumulates in postsynaptic compartment of ON-bipolar meurons in mGluR6-dependent manner. Journal of Neuroscience 31, 11521–11526.Google Scholar
Cao, Y., Sarria, I., Fehlhaber, K.E., Kamasawa, N., Orlandi, C., James, K.N., Hazen, J.L., Gardner, M.R., Farzan, M., Lee, A., Baker, S., Baldwin, K., Sampath, A.P. & Martemyanov, K.A. (2015). Mechanism for selective synaptic wiring of rod photoreceptors into the retinal circuitry and its role in vision. Neuron 87, 1248–1260.Google Scholar
Chen, C-K., Eversole-Cire, P., Zhang, H., Mancino, V., Chen, Y-J., He, W., Wensel, T.G. & Simon, M.I. (2003). Instability of GGL domain-containing RGS proteins in mice lacking the G protein β-subunit Gβ5 . Proceedings of the National Academy of Sciences of the United States of America 100, 6604–6609.Google Scholar
Dhingra, A., Faurobert, E., Dascal, N., Sterling, P. & Vardi, N. (2004). A retinal-specific regulator of G-protein signaling interacts with Gαo and accelerates an expressed metabotropic glutamate receptor 6 cascade. Journal of Neuroscience 24, 5684–5693.CrossRefGoogle ScholarPubMed
Dhingra, A., Jiang, M., Wang, T-L., Lyubarsky, A., Savchenko, A., Bar-Yehuda, T., Sterling, P., Birnbaumer, L. & Vardi, N. (2002). Light response of retinal ON bipolar cells requires a specific splice variant of Gαo . Journal of Neuroscience 22, 4878–4884.Google Scholar
Dhingra, A., Lyubarsky, A., Jiang, M., Pugh, E.N., Birnbaumer, L., Sterling, P. & Vardi, N. (2000). The light response of ON bipolar neurons requires Gαo . Journal of Neuroscience 20, 9053–9058.Google Scholar
Dhingra, A., Ramakrishnan, H., Neinstein, A., Fina, M.E., Xu, Y., Li, J., Chung, D.C., Lyubarsky, A. & Vardi, N. (2012). Gβ3 is required for normal light ON responses and synaptic maintenance. Journal of Neuroscience 32, 11343–11355.Google Scholar
Dryja, T.P., McGee, T.L., Berson, E.L., Fishman, G.A., Sandberg, M.A., Alexander, K.R., Derlacki, D.J. & Rajagopalan, A.S. (2005). Night blindness and abnormal cone electroretinogram ON responses in patients with mutations in the GRM6 gene encoding mGluR6. Proceedings of the National Academy of Sciences of the United States of America 102, 4884–4889.CrossRefGoogle ScholarPubMed
Farkas, M.H., Grant, G.R., White, J.A., Sousa, M.E., Consugar, M.B. & Pierce, E.A. (2013). Transcriptome analyses of the human retina identify unprecedented transcript diversity and 3.5 Mb of novel transcribed sequence via significant alternative splicing and novel genes. BMC Genomics 14, 486.Google Scholar
Gilliam, J.C. & Wensel, T.G. (2011). TRP channel gene expression in the mouse retina. Vision Research 51, 2440–2452.Google Scholar
Gimenez, E. & Montoliu, L. (2001). A simple polymerase chain reaction assay for genotyping the retinal degeneration mutation (Pdeb rd1) in FVB/N-derived transgenic mice. Laboratory Animals 35, 153–156.Google Scholar
Gregg, R.G., Kamermans, M., Klooster, J., Lukasiewicz, P.D., Peachey, N.S., Vessey, K.A. & McCall, M.A. (2007). Nyctalopin expression in retinal bipolar cells restores visual function in a mouse model of complete X-linked congenital stationary night blindness. Journal of Neurophysiology 98, 3023–3033.Google Scholar
Gregg, R.G., Mukhopadhyay, S., Candille, S.I., Ball, S.L., Pardue, M.T., McCall, M.A. & Peachey, N.S. (2003). Identification of the gene and the mutation responsible for the mouse nob phenotype. Investigative Ophthalmology & Visual Science 44, 378–384.CrossRefGoogle ScholarPubMed
Harper, J.W., Adami, G.R., Wei, N., Keyomarsi, K. & Elledge, S.J. (1993). The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. Cell 75, 805–816.CrossRefGoogle ScholarPubMed
Koike, C., Obara, T., Uriu, Y., Numata, T., Sanuki, R., Miyata, K., Koyasu, T., Ueno, S., Funabiki, K., Tani, A., Ueda, H., Kondo, M., Mori, Y., Tachibana, M. & Furukawa, T. (2010). TRPM1 is a component of the retinal ON bipolar cell transduction channel in the mGluR6 cascade. Proceedings of the National Academy of Sciences of the United States of America 107, 332–337.CrossRefGoogle ScholarPubMed
Koulen, P., Fletcher, E.L., Craven, S.E., Bredt, D.S. & Wassle, H. (1998). Immunocytochemical localization of the postsynaptic density protein PSD-95 in the mammalian retina. Journal of Neuroscience 18, 10136–10149.Google Scholar
Laemmli, U.K. (1970). Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227, 680–685.Google Scholar
Lambert, S., Drews, A., Rizun, O., Wagner, T.F.J., Lis, A., Mannebach, S., Plant, S., Portz, M., Meissner, M., Philipp, S.E. & Oberwinkler, J. (2011). Transient receptor potential melastatin 1 (TRPM1) is an ion-conducting plasma membrane channel inhibited by zinc. Journal of Biological Chemistry 286, 12221–12233.Google Scholar
Larkin, M.A., Blackshields, G., Brown, N.P., Chenna, R., McGettigan, P.A., McWilliam, H., Valentin, F., Wallace, I.M., Wilm, A., Lopez, R., Thompson, J.D., Gibson, T.J. & Higgins, D.G. (2007). Clustal W and Clustal X version 2.0. Bioinformatics 23, 2947–2948.CrossRefGoogle ScholarPubMed
Li, Z., Sergouniotis, P.I., Michaelides, M., Mackay, D.S., Wright, G.A., Devery, S., Moore, A.T., Holder, G.E., Robson, A.G. & Webster, A.R. (2009). Recessive mutations of the gene TRPM1 abrogate ON bipolar cell function and cause complete congenital stationary night blindness in humans. The American Journal of Human Genetics 85, 711–719.CrossRefGoogle ScholarPubMed
Lis, A., Wissenbach, U. & Philipp, S.E. (2005). Transcriptional regulation and processing increase the functional variability of TRPM channels. Naunyn-Schmiedeberg’s Archives of Pharmacology 371, 315–324.Google Scholar
Mackenzie, D., Arendt, A., Hargrave, P., McDowell, J.H. & Molday, R.S. (1984). Localization of binding sites for carboxyl terminal specific anti-rhodopsin monoclonal antibodies using synthetic peptides. Biochemistry 23, 6544–6549.Google Scholar
Maddox, D.M., Vessey, K.A., Yarbrough, G.L., Invergo, B.M., Cantrell, D.R., Inayat, S., Balannik, V., Hicks, W.L., Hawes, N.L., Byers, S., Smith, R.S., Hurd, R., Howell, D., Gregg, R.G., Chang, B., Naggert, J.K., Troy, J.B., Pinto, L.H., Nishina, P.M. & McCall, M.A. (2008). Allelic variance between GRM6 mutants, Grm6 nob3 and Grm6 nob4 results in differences in retinal ganglion cell visual responses. The Journal of Physiology 586, 4409–4424.Google Scholar
Masu, M., Iwakabe, H., Tagawa, Y., Miyoshi, T., Yamashita, M., Fukuda, Y., Sasaki, H., Hiroi, K., Nakamura, Y., Shigemoto, R., Takada, M., Nakamura, K., Nakao, K., Katsuki, M. & Nakanishi, S. (1995). Specific deficit of the ON response in visual transmission by targeted disruption of the mGluR6 gene. Cell 80, 757–765.Google Scholar
Mattapallil, M.J., Wawrousek, E.F., Chan, C-C., Zhao, H., Roychoudhury, J., Ferguson, T.A. & Caspi, R.R. (2012). The rd8 mutation of the Crb1 gene is present in vendor lines of C57BL/6N mice and embryonic stem cells, and confounds ocular induced mutant phenotypes. Investigative Ophthalmology & Visual Science 53, 2921–2927.Google Scholar
Mojumder, D.K., Qian, Y. & Wensel, T.G. (2009). Two R7 regulator of G-protein signaling proteins shape retinal bipolar cell signaling. Journal of Neuroscience 29, 7753–7765.Google Scholar
Morgans, C.W., Ren, G. & Akileswaran, L. (2006). Localization of nyctalopin in the mammalian retina. European Journal of Neuroscience 23, 1163–1171.Google Scholar
Morgans, C.W., Zhang, J., Jeffrey, B.G., Nelson, S.M., Burke, N.S., Duvoisin, R.M. & Brown, R.L. (2009). TRPM1 is required for the depolarizing light response in retinal ON-bipolar cells. Proceedings of the National Academy of Sciences of the United States of America 106, 19174–19178.Google Scholar
Mustafi, D., Kevany, B.M., Bai, X., Golczak, M., Adams, M.D., Wynshaw-Boris, A. & Palczewski, K. (2016). Transcriptome analysis reveals rod/cone photoreceptor specific signatures across mammalian retinas. Human Molecular Genetics 25, 4376–4388.Google Scholar
Mustafi, D., Kevany, B.M., Genoud, C., Okano, K., Cideciyan, A.V., Sumaroka, A., Roman, A.J., Jacobson, S.G., Engel, A., Adams, M.D. & Palczewski, K. (2011). Defective photoreceptor phagocytosis in a mouse model of enhanced S-cone syndrome causes progressive retinal degeneration. The FASEB Journal 25, 3157–3176.Google Scholar
Nakajima, Y., Iwakabe, H., Akazawa, C., Nawa, H., Shigemoto, R., Mizuno, N. & Nakanishi, S. (1993). Molecular characterization of a novel retinal metabotropic glutamate receptor mGluR6 with a high agonist selectivity for L-2-amino-4-phosphonobutyrate. Journal of Biological Chemistry 268, 11868–11873.Google Scholar
Neuillé, M., Morgans, C.W., Cao, Y., Orhan, E., Michiels, C., Sahel, J-A., Audo, I., Duvoisin, R.M., Martemyanov, K.A. & Zeitz, C. (2015). LRIT3 is essential to localize TRPM1 to the dendritic tips of depolarizing bipolar cells and may play a role in cone synapse formation. European Journal of Neuroscience 42, 1966–1975.Google Scholar
Neuillé, M., El Shamieh, S., Orhan, E., Michiels, C., Antonio, A., Lancelot, M-E., Condroyer, C., Bujakowska, K., Poch, O., Sahel, J-A., Audo, I. & Zeitz, C. (2014). Lrit3 deficient mouse (nob6): A novel model of complete congenital stationary night blindness (cCSNB). PLos One 9, e90342.Google Scholar
Nomura, A., Shigemoto, R., Nakamura, Y., Okamoto, N., Mizuno, N. & Nakanishi, S. (1994). Developmentally regulated postsynaptic localization of a metabotropic glutamate receptor in rat rod bipolar cells. Cell 77, 361–369.Google Scholar
Oancea, E., Vriens, J., Brauchi, S., Jun, J., Splawski, I. & Clapham, D.E. (2009). TRPM1 forms ion channels associated with melanin content in melanocytes. Science Signaling 2, ra21.Google Scholar
Oberwinkler, J., Lis, A., Giehl, K.M., Flockerzi, V. & Philipp, S.E. (2005). Alternative splicing switches the divalent cation selectivity of TRPM3 channels. Journal of Biological Chemistry 280, 22540–22548.Google Scholar
Orlandi, C., Cao, Y. & Martemyanov, K.A. (2013). Orphan receptor GPR179 forms macromolecular complexes with components of metabotropic signaling cascade in retina ON-bipolar neurons. Investigative Ophthalmology & Visual Science 54, 7153–7161.Google Scholar
Peachey, N.S., Ray, T.A., Florijn, R., Rowe, L.B., Sjoerdsma, T., Contreras-Alcantara, S., Baba, K., Tosini, G., Pozdeyev, N., Iuvone, P.M., Bojang, P., Pearring, J.N., Simonsz, H.J., van Genderen, M., Birch, D.G., Traboulsi, E.I., Dorfman, A., Lopez, I., Ren, H., Goldberg, A.F.X., Nishina, P.M., Lachapelle, P., McCall, M.A., Koenekoop, R.K., Bergen, A.A.B., Kamermans, M. & Gregg, R.G. (2012). GPR179 is required for depolarizing bipolar cell function and is mutated in autosomal-recessive complete congenital stationary night blindness. The American Journal of Human Genetics 90, 331–339.Google Scholar
Pearring, J.N., Bojang, P. Jr., Shen, Y., Koike, C., Furukawa, T., Nawy, S. & Gregg, R.G. (2011). A role for nyctalopin, a small leucine-rich repeat protein, in localizing the TRP melastatin 1 channel to retinal depolarizing bipolar cell dendrites. Journal of Neuroscience 31, 10060–10066.CrossRefGoogle ScholarPubMed
Pusch, C.M., Zeitz, C., Brandau, O., Pesch, K., Achatz, H., Feil, S., Scharfe, C., Maurer, J., Jacobi, F.K., Pinckers, A., Andreasson, S., Hardcastle, A., Wissinger, B., Berger, W. & Meindl, A. (2000). The complete form of X-linked congenital stationary night blindness is caused by mutations in a gene encoding a leucine-rich repeat protein. Nature Genetics 26, 324–327.Google Scholar
Rao, A., Dallman, R., Henderson, S. & Chen, C-K. (2007). Gβ5 Is required for normal light responses and morphology of retinal ON-bipolar cells. Journal of Neuroscience 27, 14199–14204.CrossRefGoogle ScholarPubMed
Ray, T.A., Heath, K.M., Hasan, N., Noel, J.M., Samuels, I.S., Martemyanov, K.A., Peachey, N.S., McCall, M.A. & Gregg, R.G. (2014). GPR179 Is required for high sensitivity of the mGluR6 signaling cascade in depolarizing bipolar cells. Journal of Neuroscience 34, 6334–6343.Google Scholar
Scott, D.B., Blanpied, T.A. & Ehlers, M.D. (2003). Coordinated PKA and PKC phosphorylation suppresses RXR-mediated ER retention and regulates the surface delivery of NMDA receptors. Neuropharmacology 45, 755–767.Google Scholar
Shen, Y., Heimel, J.A., Kamermans, M., Peachey, N.S., Gregg, R.G. & Nawy, S. (2009). A transient receptor potential-like channel mediates synaptic transmission in rod bipolar cells. Journal of Neuroscience 29, 6088–6093.Google Scholar
Shen, Y., Rampino, M.A.F., Carroll, R.C. & Nawy, S. (2012). G-protein–mediated inhibition of the Trp channel TRPM1 requires the Gβγ dimer. Proceedings of the National Academy of Sciences of the United States of America 109, 8752–8757.Google Scholar
Shim, H., Wang, C-T., Chen, Y-L., Chau, V.Q., Fu, K.G., Yang, J., McQuiston, A.R., Fisher, R.A. & Chen, C-K. (2012). Defective retinal depolarizing bipolar cells in regulators of G protein signaling (RGS) 7 and 11 double null mice. Journal of Biological Chemistry 287, 14873–14879.Google Scholar
Sievers, F., Wilm, A., Dineen, D., Gibson, T.J., Karplus, K., Li, W., Lopez, R., McWilliam, H., Remmert, M., Soding, J., Thompson, J.D. & Higgins, D.G. (2011). Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Molecular Systems Biology 7, 539.Google Scholar
Van Genderen, M.M., Bijveld, M.M.C., Claassen, Y.B., Florijn, R.J., Pearring, J.N., Meire, F.M., Mccall, M.A., Riemslag, F.C.C., Gregg, R.G., Bergen, A.A.B. & Kamermans, M. (2009). Mutations in TRPM1 are a common cause of complete congenital stationary night blindness. The American Journal of Human Genetics 85, 730–736.Google Scholar
VanGuilder, H.D., Brucklacher, R.M., Patel, K., Ellis, R.W., Freeman, W.M. & Barber, A.J. (2008). Diabetes downregulates presynaptic proteins and reduces basal synapsin I phosphorylation in rat retina. European Journal of Neuroscience 28, 1–11.Google Scholar
Xu, X.S., Moebius, F., Gill, D.L. & Montell, C. (2001). Regulation of melastatin, a TRP-related protein, through interaction with a cytoplasmic isoform. Proceedings of the National Academy of Sciences of the United States of America 98, 10692–10697.Google Scholar
Zeitz, C., van Genderen, M., Neidhardt, J., Luhmann, U.F.O., Hoeben, F., Forster, U., Wycisk, K., Mátyás, G., Hoyng, C.B., Riemslag, F., Meire, F., Cremers, F.P.M. & Berger, W. (2005). Mutations in GRM6 cause autosomal recessive congenital stationary night blindness with a distinctive scotopic 15 Hz flicker electroretinogram. Investigative Ophthalmology & Visual Science 46, 4328–4335.CrossRefGoogle ScholarPubMed
Zeitz, C., Jacobson, S.G., Hamel, C.P., Bujakowska, K., Neuille, M., Orhan, E., Zanlonghi, X., Lancelot, M., Michiels, C., Schwartz, S.B., Bocquet, B., Antonio, A., Audier, C., Letexier, M., Saraiva, J., Luu, T.D., Sennlaub, F., Nguyen, H., Lecompte, O., Poch, O., Dollfus, H., Kohl, S., Sahel, J-A., Bhattacharya, S.S. & Audo, I. (2013). Whole-exome sequencing identifies LRIT3 mutations as a cause of autosomal-recessive complete congenital stationary night blindness. The American Journal of Human Genetics 92, 67–75.Google Scholar