Molecular and Functional Characterization of the Melastatin-related Cation Channel TRPM3

Grimm, Christian; Kraft, Robert A.; Sauerbruch, Sophie; Schultz, Günter; Harteneck, Christian

doi:10.1074/jbc.m300945200

Cited by 318 publications

(327 citation statements)

References 29 publications

(48 reference statements)

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“…miR-204 was detected in RNA from the choroid plexus, but not the cerebral cortex, whereas the neural-specific miR-124a was detected in the cortex and not the choroid plexus. miR-204 is located within the sixth intron of the transient receptor potential melastatin 3 (TRPM3) cation channel and is transcribed in the same direction as TRPM3 (Grimm et al, 2003;Lagos-Quintana et al, 2003;Rodriguez et al, 2004). TRPM3 is expressed in choroid plexus and eye (Oberwinkler et al, 2005).…”

Section: Resultsmentioning

confidence: 99%

“…The miR-204 miRNA is located in the intron of the TRPM3 gene, and TRPM3 is also expressed in the choroid plexus, suggesting that the miRNA and TRPM3 are derived from a single transcription unit in that tissue. TRPM3 encodes a cation channel, but its biological function is not known (Grimm et al, 2003;Oberwinkler et al, 2005). A subset of miRNAs is located within the introns of protein coding genes (Rodriguez et al, 2004), and analysis of microarray data has shown that the expression of several intronic miRNAs is correlated with the expression of the mRNA from the same locus (Baskerville and Bartel, 2005).…”

Section: Discussionmentioning

confidence: 99%

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Detection of mammalian microRNA expression by in situ hybridization with RNA oligonucleotides

Deo

Chung

et al. 2006

Developmental Dynamics

268

216

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We have developed an in situ hybridization procedure for the detection of microRNAs (miRNAs) in tissue sections from mouse embryos and adult organs. The method uses highly specific washing conditions for RNA oligonucleotide probes conjugated to a fluorescein hapten. We show that this method detects predominantly mature miRNAs rather than the miRNA precursors or primary transcripts. We have determined expression patterns for several miRNAs expressed in the developing and adult nervous system, including miR-124a, miR-9, miR-92, and miR-204. Whereas miR-124a is expressed in neurons, miR-9 is expressed in neural progenitors and some neurons, and miR-204 is expressed in the choroid plexus, retinal pigment epithelium, and ciliary body. miR-204 is located in an intron of the TRPM3 gene, and the TRPM3 mRNA is coexpressed with miR-204 in the choroid plexus. We also find that primary transcripts for miR-124a and miR-9 genes are expressed in patterns similar to their respective mature miRNAs. The ability to visualize expression of specific miRNAs in embryos and tissues should aid studies on miRNA function.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Detection of mammalian microRNA expression by in situ hybridization with RNA oligonucleotides

Deo

Chung

et al. 2006

Developmental Dynamics

268

216

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“…Thus, TRPM2, TRPM3 and TRPM8 are Ca 2+ permeable nonselective cation channels, which differ substantially with respect to their activation stimuli (Chuang et al 2004;Grimm et al 2003;Hara et al 2002;Lee et al 2003;McKemy et al 2002;Peier et al 2002;Sano et al 2001;Wehage et al 2002). TRPM8 is activated by low temperature (Chuang et al 2004;Voets et al 2004a), while TRPM2 is stimulated by intracellular ADP-ribose, NAD + and oxidative stress (Hara et al 2002;Perraud et al 2001Perraud et al , 2003).…”

Section: Introductionmentioning

confidence: 99%

“…TRPM8 is activated by low temperature (Chuang et al 2004;Voets et al 2004a), while TRPM2 is stimulated by intracellular ADP-ribose, NAD + and oxidative stress (Hara et al 2002;Perraud et al 2001Perraud et al , 2003). TRPM3 appears to be activated by hypoosmotic cell swelling, rises of intracellular Ca 2+ and by D-erythro-sphingosine (Grimm et al 2003(Grimm et al , 2004Lee et al 2003). Two other TRPM subfamily members, TRPM4 and TRPM5, are mainly permeable for monovalent cations, gated by increases in intracellular Ca 2+ and exhibit a pronounced voltage modulation (Hofmann et al 2003;Launay et al 2002;Liu and Liman, 2003;Nilius et al 2003;Prawitt et al 2003).…”

Section: Introductionmentioning

confidence: 99%

Emerging roles of TRPM6/TRPM7 channel kinase signal transduction complexes

Chubanov

Schnitzler

Wäring

et al. 2005

Naunyn-Schmiedeberg's Arch Pharmacol

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Investigations into Drosophila mutants with impaired vision due to mutations in the transient receptor potential gene (trp) initiated a systematic search for TRP homologs in other species, finally leading to the discovery of a whole new family of plasma membrane cation channels involved in multiple physiological processes. Among the recently discovered TRP cation channels two homologous proteins, TRPM6 and TRPM7, display unique domain compositions and biophysical properties. These remarkable genes are vital for Mg 2+ homeostasis in vertebrates and, if disrupted, lead to cell death or human disease.

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“…To exclude that the individual proline substitutions led to channel inactivation, functional tests of the mutant channels were performed by using specific agonists. TRPV2 mutants were gated with diphenyl boronic anhydride (DPBA) (12), and TRPC6 mutants were gated with 1,2-didecanoyl-glycerol (DDG) (13,14) in calcium imaging experiments; TRPM2 mutant gating was tested in patch-clamp experiments using ADP-ribose (15, 16) (SI Fig. 8 C-E).…”

Section: Tm5 Susceptibility Is a General Feature Of Trpmls As Well Asmentioning

confidence: 99%

A helix-breaking mutation in TRPML3 leads to constitutive activity underlying deafness in the varitint-waddler mouse

Cuajungco

Aken

Schnee

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Homozygote varitint-waddler (Va) mice, expressing a mutant isoform (A419P) of TRPML3 (mucolipin 3), are profoundly deaf and display vestibular and pigmentation deficiencies, sterility, and perinatal lethality. Here we show that the varitint-waddler isoform of TRPML3 carrying an A419P mutation represents a constitutively active cation channel that can also be identified in native varitintwaddler hair cells as a distinct inwardly rectifying current. We hypothesize that the constitutive activation of TRPML3 occurs as a result of a helix-breaking proline substitution in transmembranespanning domain 5 (TM5). A proline substitution scan demonstrated that the inner third of TRPML3's TM5 is highly susceptible to proline-based kinks. Proline substitutions in TM5 of other TRP channels revealed that TRPML1, TRPML2, TRPV5, and TRPV6 display a similar susceptibility at comparable positions, whereas other TRP channels were not affected. We conclude that the molecular basis for deafness in the varitint-waddler mouse is the result of hair cell death caused by constitutive TRPML3 activity. To our knowledge, our study provides the first direct mechanistic link of a mutation in a TRP ion channel with mammalian hearing loss.cation channel ͉ cochlea ͉ hair cell ͉ inner ear ͉ TRP channel T ransient receptor potential (TRP) cation channels are important components of many cellular and sensory systems, such as osmosensation, photosensation, taste sensation, and thermosensation (1, 2). In Drosophila, Caenorhabditis elegans, and lower vertebrates, mutations in TRP channels have also been associated with loss of sensitivity to touch and other forms of mechanical stimulation (3-5). Besides the general notion that they conduct cations, TRP channels have quite diverse structural and functional properties (1, 2).The identification of mutations in the human mucolipin (TRPML1) gene as the cause of mucolipidosis type IV, a neurodegenerative, recessive, lysosomal storage disorder characterized by psychomotor retardation and visual impairment, led to the initial description of the TRPML subfamily (6, 7). The mammalian TRPML subfamily consists of three members: TRPML1, TRPML2, and TRPML3. Like other TRP channels TRPML proteins contain six putative transmembrane domains with cytosolic amino and carboxyl termini. A mutant isoform of murine Trpml3 has recently been identified as the underlying cause of the varitint-waddler (Va) phenotype that is manifested in profound deafness, vestibular defects, pigmentation deficiencies, sterility, and perinatal lethality (8, 9). The Trpml3 (Va) allele displays an alanine to proline substitution at amino acid position 419 (A419P) in the fifth transmembrane domain of TRPML3 (8) [supporting information (SI) Fig. 5]. A second amino acid substitution (I362T) positioned at the second extracellular loop arose in cis to A419P, resulting in the Va J allele that attenuates and partially rescues the severe Va phenotype by an unknown mechanism.The present work was conducted to determine the specific role of the varitint-waddl...

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Molecular and Functional Characterization of the Melastatin-related Cation Channel TRPM3

Cited by 318 publications

References 29 publications

Detection of mammalian microRNA expression by in situ hybridization with RNA oligonucleotides

Detection of mammalian microRNA expression by in situ hybridization with RNA oligonucleotides

Emerging roles of TRPM6/TRPM7 channel kinase signal transduction complexes

A helix-breaking mutation in TRPML3 leads to constitutive activity underlying deafness in the varitint-waddler mouse

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