Regulation of melastatin, a TRP-related protein, through interaction with a cytoplasmic isoform

The TRP (transient receptor potential) superfamily includes a group of subfamilies of channel-like proteins mediating a multitude of physiological signaling processes. The TRP-melastatin (TRPM) subfamily includes the putative tumor suppressor melastatin (MLSN) and is a poorly characterized group of TRP-related proteins. Here, we describe the identification and characterization of an additional TRPM protein TRPM4. We reveal that TRPM4 and MLSN each mediate Ca2+ entry when expressed in HEK293 cells. Furthermore, we demonstrate that a short form of MLSN (MLSN-S) interacts directly with and suppresses the activity of full-length MLSN (MLSN-L). This suppression seems to result from the inhibition of translocation of MLSN-L to the plasma membrane. We propose that control of translocation through interaction between MLSN-S and MLSN-L represents a mode for regulating ion channel activity.

[1]  G. Rubin,et al.  Molecular characterization of the drosophila trp locus: A putative integral membrane protein required for phototransduction , 1989, Neuron.

[2]  R. Hardie,et al.  The trp gene is essential for a light-activated Ca2+ channel in Drosophila photoreceptors , 1992, Neuron.

[3]  Cori Bargmann,et al.  OSM-9, A Novel Protein with Structural Similarity to Channels, Is Required for Olfaction, Mechanosensation, and Olfactory Adaptation inCaenorhabditis elegans , 1997, The Journal of Neuroscience.

[4]  C. Montell,et al.  Coassembly of TRP and TRPL Produces a Distinct Store-Operated Conductance , 1997, Cell.

[5]  N. Shimizu,et al.  Molecular cloning of a novel putative Ca2+ channel protein (TRPC7) highly expressed in brain. , 1998, Genomics.

[6]  L M Duncan,et al.  Down-regulation of the novel gene melastatin correlates with potential for melanoma metastasis. , 1998, Cancer research.

[7]  J. Hunter,et al.  Chromosomal localization and genomic characterization of the mouse melastatin gene (Mlsn1). , 1998, Genomics.

[8]  Y. Mori,et al.  Molecular and Functional Characterization of a Novel Mouse Transient Receptor Potential Protein Homologue TRP7 , 1999, The Journal of Biological Chemistry.

[9]  C. Montell,et al.  Visual transduction in Drosophila. , 1999, Annual review of cell and developmental biology.

[10]  L. Salkoff,et al.  TRPγ, a Drosophila TRP–Related Subunit, Forms a Regulated Cation Channel with TRPL , 2000, Neuron.

[11]  S. Bingham,et al.  Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia , 2000, Nature.

[12]  G. Schultz,et al.  OTRPC4, a nonselective cation channel that confers sensitivity to extracellular osmolarity , 2000, Nature Cell Biology.

[13]  C. Zuker,et al.  A Drosophila mechanosensory transduction channel. , 2000, Science.

[14]  A. Winterpacht,et al.  Mtr1, a novel biallelically expressed gene in the center of the mouse distal chromosome 7 imprinting cluster, is a member of the Trp gene family. , 2000, Genomics.

[15]  M. Freichel,et al.  Trp12, a novel Trp related protein from kidney , 2000, FEBS letters.

[16]  J. Deeds,et al.  Patterns of melastatin mRNA expression in melanocytic tumors. , 2000, Human pathology.

[17]  A. Hudspeth,et al.  Vanilloid Receptor–Related Osmotically Activated Channel (VR-OAC), a Candidate Vertebrate Osmoreceptor , 2000, Cell.

[18]  V. Setaluri,et al.  Expression and Up-regulation of alternatively spliced transcripts of melastatin, a melanoma metastasis-related gene, in human melanoma cells. , 2000, Biochemical and biophysical research communications.

[19]  J. Pelletier,et al.  Identification and characterization of MTR1, a novel gene with homology to melastatin (MLSN1) and the trp gene family located in the BWS-WT2 critical region on chromosome 11p15.5 and showing allele-specific expression. , 2000, Human molecular genetics.

[20]  A I Basbaum,et al.  Impaired nociception and pain sensation in mice lacking the capsaicin receptor. , 2000, Science.

[21]  G. Schultz,et al.  From worm to man: three subfamilies of TRP channels , 2000, Trends in Neurosciences.

[22]  D. Clapham,et al.  TRP-PLIK, a Bifunctional Protein with Kinase and Ion Channel Activities , 2001, Science.

[23]  A. Perraud,et al.  ADP-ribose gating of the calcium-permeable LTRPC2 channel revealed by Nudix motif homology , 2001, Nature.

[24]  A. Sober,et al.  Melastatin expression and prognosis in cutaneous malignant melanoma. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[25]  M. Biel,et al.  Lack of an endothelial store-operated Ca2+ current impairs agonist-dependent vasorelaxation in TRP4−/− mice , 2001, Nature Cell Biology.

[26]  M. Nadler,et al.  LTRPC7 is a Mg·ATP-regulated divalent cation channel required for cell viability , 2001, Nature.

[27]  R. J. West,et al.  The C. elegans gon-2 gene encodes a putative TRP cation channel protein required for mitotic cell cycle progression. , 2001, Gene.