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 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.
Xu
X Z
XZ
Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Moebius
F
F
Gill
D L
DL
Montell
C
C
D000595:Amino Acid Sequence; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D027682:Cation Transport Proteins; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D020033:Protein Isoforms / Q000378:metabolism; D050053:TRPM Cation Channels
D015220:Calcium Channels; D027682:Cation Transport Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D050053:TRPM Cation Channels; C492059:TRPM1 protein, human; C437888:TRPM4 protein, human; D002118:Calcium