Home LiteratureArticle Details
PMID: 11535825 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

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

Xu XZ, Moebius F, Gill DL, Montell C

Abstract

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 Ca(2+) 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.

MeSH Terms
Amino Acid Sequence Calcium/metabolism Calcium Channels/genetics,metabolism Cation Transport Proteins Cell Line Cytoplasm/metabolism Humans Membrane Proteins/genetics,metabolism Molecular Sequence Data Neoplasm Proteins Protein Isoforms/metabolism TRPM Cation Channels
Chemicals
Calcium Channels Cation Transport Proteins Membrane Proteins Neoplasm Proteins Protein Isoforms TRPM Cation Channels TRPM1 protein, human TRPM4 protein, human Calcium
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Xu X Z
Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Moebius F
Gill D L
Montell C
References (28)
28 references, click to expand
  1. The trp gene is essential for a light-activated Ca2+ channel in Drosophila photoreceptors.
    Neuron. 1992 Apr;8(4):643-51 PMID: 1314617
  2. Molecular characterization of the Drosophila trp locus: a putative integral membrane protein required for phototransduction.
    Neuron. 1989 Apr;2(4):1313-23 PMID: 2516726
  3. OSM-9, a novel protein with structural similarity to channels, is required for olfaction, mechanosensation, and olfactory adaptation in Caenorhabditis elegans.
    J Neurosci. 1997 Nov 1;17(21):8259-69 PMID: 9334401
  4. Down-regulation of the novel gene melastatin correlates with potential for melanoma metastasis.
    Cancer Res. 1998 Apr 1;58(7):1515-20 PMID: 9537257
  5. Chromosomal localization and genomic characterization of the mouse melastatin gene (Mlsn1).
    Genomics. 1998 Nov 15;54(1):116-23 PMID: 9806836
  6. Molecular cloning of a novel putative Ca2+ channel protein (TRPC7) highly expressed in brain.
    Genomics. 1998 Nov 15;54(1):124-31 PMID: 9806837
  7. Molecular and functional characterization of a novel mouse transient receptor potential protein homologue TRP7. Ca(2+)-permeable cation channel that is constitutively activated and enhanced by stimulation of G protein-coupled receptor.
    J Biol Chem. 1999 Sep 24;274(39):27359-70 PMID: 10488066
  8. 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.
    Hum Mol Genet. 2000 Jan 22;9(2):203-16 PMID: 10607831
  9. Visual transduction in Drosophila.
    Annu Rev Cell Dev Biol. 1999;15:231-68 PMID: 10611962
  10. From worm to man: three subfamilies of TRP channels.
    Trends Neurosci. 2000 Apr;23(4):159-66 PMID: 10717675
  11. A Drosophila mechanosensory transduction channel.
    Science. 2000 Mar 24;287(5461):2229-34 PMID: 10744543
  12. Impaired nociception and pain sensation in mice lacking the capsaicin receptor.
    Science. 2000 Apr 14;288(5464):306-13 PMID: 10764638
  13. Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia.
    Nature. 2000 May 11;405(6783):183-7 PMID: 10821274
  14. TRPgamma, a drosophila TRP-related subunit, forms a regulated cation channel with TRPL.
    Neuron. 2000 Jun;26(3):647-57 PMID: 10896160
  15. 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.
    Genomics. 2000 Jul 15;67(2):179-87 PMID: 10903843
  16. OTRPC4, a nonselective cation channel that confers sensitivity to extracellular osmolarity.
    Nat Cell Biol. 2000 Oct;2(10):695-702 PMID: 11025659
  17. Vanilloid receptor-related osmotically activated channel (VR-OAC), a candidate vertebrate osmoreceptor.
    Cell. 2000 Oct 27;103(3):525-35 PMID: 11081638
  18. Trp12, a novel Trp related protein from kidney.
    FEBS Lett. 2000 Nov 24;485(2-3):127-34 PMID: 11094154
  19. Expression and Up-regulation of alternatively spliced transcripts of melastatin, a melanoma metastasis-related gene, in human melanoma cells.
    Biochem Biophys Res Commun. 2000 Dec 9;279(1):53-61 PMID: 11112417
  20. Patterns of melastatin mRNA expression in melanocytic tumors.
    Hum Pathol. 2000 Nov;31(11):1346-56 PMID: 11112208
  21. TRP-PLIK, a bifunctional protein with kinase and ion channel activities.
    Science. 2001 Feb 9;291(5506):1043-7 PMID: 11161216
  22. Lack of an endothelial store-operated Ca2+ current impairs agonist-dependent vasorelaxation in TRP4-/- mice.
    Nat Cell Biol. 2001 Feb;3(2):121-7 PMID: 11175743
  23. Melastatin expression and prognosis in cutaneous malignant melanoma.
    J Clin Oncol. 2001 Jan 15;19(2):568-76 PMID: 11208852
  24. The C. elegans gon-2 gene encodes a putative TRP cation channel protein required for mitotic cell cycle progression.
    Gene. 2001 Mar 21;266(1-2):103-10 PMID: 11290424
  25. LTRPC7 is a Mg.ATP-regulated divalent cation channel required for cell viability.
    Nature. 2001 May 31;411(6837):590-5 PMID: 11385574
  26. ADP-ribose gating of the calcium-permeable LTRPC2 channel revealed by Nudix motif homology.
    Nature. 2001 May 31;411(6837):595-9 PMID: 11385575
  27. Physiology, phylogeny, and functions of the TRP superfamily of cation channels.
    Sci STKE. 2001 Jul 10;2001(90):re1 PMID: 11752662
  28. Coassembly of TRP and TRPL produces a distinct store-operated conductance.
    Cell. 1997 Jun 27;89(7):1155-64 PMID: 9215637
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
2001-09-11
Epub
2001-00-04
Pages
10692-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC58528
Subset
IM
Grants
NEI NIH HHS · R01 EY010852 · United States
NEI NIH HHS · EY10852 · United States
Databases
GENBANK
AY046396
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com