Abstract
TRPML2, the polypeptide product of the gene Trpml2 (aka Mcoln2), is a member of the TRPML or mucolipin branch of the TRP super family of ion channels. Although no known agonists have been discovered, the wild type channel gives basal currents when heterologously expressed in Drosophila (S2) cells and is constitutively active in mammalian cells when bearing a cell degeneration-causing, proline to alanine substitution in the fifth trans-membrane domain. TRPML2 forms channels that are inwardly rectifying and permeable to Ca +2, Na +, and Fe +2. Localization studies indicate TRPML2 is present in lysosomes, late endosomes, recycling endosomes and, at a lower level, the plasma membrane. Tissue and organ distribution of TRPML2 is solely reported through RT-PCR and it is uncertain which cell types express this channel. However, various studies suggest that lymphoid cells express TRPML2. Although the function of TRPML2 is not known, distribution and channel properties suggest it could play roles in calcium release from endolysosomes, perhaps to mediate calcium-dependent events such as vesicle fusion, or to release calcium from intracellular acidic stores. However, TRPML2 may also function in the plasma membrane and its abundance in vesicles of the endocytic pathaway might occur because its presence in the cell surface is regulated by endocytosis and exocytosis. An evolutionary analysis of Trpml2 and its relatives reveals that vertebrate and invertebrate chordates have only one Trpml gene, that Trpml1 and Trpml2 are common to vertebrates, and that Trpml3 is only found in tetrapods. Ray-finned fishes contain another isoform, which we term Trpml4 or Mcoln4 (and its product TRPML4). Trpml2 is next to Trpml3 in all tetrapod genomes except that of the frog Xenopus tropicalis and of the domesticated pig, which seems to lack most of the Trpml3 gene. This close linkage across species implies that it is maintained by selective pressure and suggests that the regulation of both genes is interdependent.
Original language | English (US) |
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Title of host publication | Transient Receptor Potential Channels |
Editors | Shahidul Islam, Shahidul Islam |
Pages | 221-228 |
Number of pages | 8 |
DOIs | |
State | Published - 2011 |
Publication series
Name | Advances in Experimental Medicine and Biology |
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Volume | 704 |
ISSN (Print) | 0065-2598 |
Funding
Supported by grants from NIH-NINDS (R01 NS044363), NIH-NIAMS (P30 AR057216) and The Hugh Knowles Center for Clinical and Basic Science in Hearing and Its Disorders to JG-A.
Keywords
- Channel
- Channel evolution
- Endosome
- Lymphocyte
- Lysosome
- Mcoln
- Mucolipin
- TRPML
- TRPML2
- TRPML3
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology