TRPML2 and the evolution of mucolipins

Emma N. Flores, Jaime Garcia-Anoveros*

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingConference contribution

8 Citations (Scopus)

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 languageEnglish (US)
Title of host publicationTransient Receptor Potential Channels
EditorsShahidul Islam, Shahidul Islam
Pages221-228
Number of pages8
DOIs
StatePublished - Dec 15 2011

Publication series

NameAdvances in Experimental Medicine and Biology
Volume704
ISSN (Print)0065-2598

Fingerprint

Genes
Endosomes
Cell membranes
Calcium
Vertebrates
Nonvertebrate Chordata
Bearings (structural)
Skates (Fish)
Cell Membrane
Transport Vesicles
Exocytosis
Tissue Distribution
Xenopus
Endocytosis
Lysosomes
Ion Channels
Proline
Alanine
Anura
Fish

Keywords

  • Channel
  • Channel evolution
  • Endosome
  • Lymphocyte
  • Lysosome
  • Mcoln
  • Mucolipin
  • TRPML
  • TRPML2
  • TRPML3

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Flores, E. N., & Garcia-Anoveros, J. (2011). TRPML2 and the evolution of mucolipins. In S. Islam, & S. Islam (Eds.), Transient Receptor Potential Channels (pp. 221-228). (Advances in Experimental Medicine and Biology; Vol. 704). https://doi.org/10.1007/978-94-007-0265-3_12
Flores, Emma N. ; Garcia-Anoveros, Jaime. / TRPML2 and the evolution of mucolipins. Transient Receptor Potential Channels. editor / Shahidul Islam ; Shahidul Islam. 2011. pp. 221-228 (Advances in Experimental Medicine and Biology).
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Flores, EN & Garcia-Anoveros, J 2011, TRPML2 and the evolution of mucolipins. in S Islam & S Islam (eds), Transient Receptor Potential Channels. Advances in Experimental Medicine and Biology, vol. 704, pp. 221-228. https://doi.org/10.1007/978-94-007-0265-3_12

TRPML2 and the evolution of mucolipins. / Flores, Emma N.; Garcia-Anoveros, Jaime.

Transient Receptor Potential Channels. ed. / Shahidul Islam; Shahidul Islam. 2011. p. 221-228 (Advances in Experimental Medicine and Biology; Vol. 704).

Research output: Chapter in Book/Report/Conference proceedingConference contribution

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N2 - 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.

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Flores EN, Garcia-Anoveros J. TRPML2 and the evolution of mucolipins. In Islam S, Islam S, editors, Transient Receptor Potential Channels. 2011. p. 221-228. (Advances in Experimental Medicine and Biology). https://doi.org/10.1007/978-94-007-0265-3_12