Transient receptor potential (TRP) cation channels play key roles in maintaining intracellular calcium homeostasis. High levels of intracellular calcium are cytotoxic; the dysregulation of calcium homeostasis is involved in the pathogenesis of a number of neurodegenerative diseases. There are many genes encoding TRP channels in both human (28 described, see link below) and Drosophila (13 described, see link below). The Drosophila TRP channel gene trp has been used to model calcium-induced neurotoxicity in flies. Classical loss-of-function alleles, RNAi targeting constructs, and alleles caused by insertional mutagenesis have been generated for Dmel\trp.
Dmel\trp is most closely related to the human genes TRPC1, TRPC4, and TRPC5. None of these human genes has been introduced into flies.
Dmel\trp is expressed primarily in the adult eye and contributes to the electrical response to light in photoreceptors. A constitutively active form of trp results in increased levels of cellular calcium and retinal degeneration; photoreceptor cells contain morphologically abnormal mitochondria. This system has been used to investigate the mechanisms by which elevated cellular calcium causes cell death. The retinal degeneration phenotype is ameliorated by genetic activation of autophagy, including overexpression of genes implicated in Parkinson disease (PARK 2, FBhh0000008; PARK6, FBhh0000009). Many physical and genetic interactions of Dmel\trp have been described; see below and in the trp gene report.
A constitutively active form of Dmel\trp, trpP365, has been used extensively. There are 4 missense mutations associated with this allele: P500T, H531N, F550I, S867F. Of these sites, F550 is located within the beginning of the predicted S5 transmembrane domain and is highly conserved in TRP channels. A mutation in mouse in the TRPML gene and mutations in the human TRPV4 gene implicated in brachyolmia map within the same conserved region (Myer et al., 2008; pubmed:18955590).
See also the human disease model report 'mitochondrial disorders, VDAC-related' (FBhh0000722).
[updated Feb. 2018 by FlyBase; FBrf0222196]