This report describes a general model of neuromuscular disease, JPH (junctophilin)-related. Junctophilins are structural components of junctional complexes between the plasma membrane and endoplasmic/sarcoplasmic reticulum and are required for functional crosstalk between cell-surface and intracellular ion channels. There are four junctophilins in human; they exhibit differential tissue-specific expression. Three of the human genes are implicated in disease (see MIM:606438, HDL2, FBhh0000820; OMIM;613873, CMH17, FBhh0000821; MIM:607831, CMT2K, FBhh0000091). There is a single junctophilin in Drosophila, jp, for which RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated.
None of the human junctophilin genes has been introduced into flies.
Broad embryonic expression of RNAi directed against jp results in lethality. Later tissue-specific up- or downregulation of jp results in a spectrum of adult phenotypes characterized by locomotor deficits, muscle cellular structure defects, dilated cardiomyopathy, neuronal defects, and 'bang sensitivity'. Assayed in the eye, up- or downregulation of jp results in amelioration or exacerbation, respectively, of phenotypes produced by models of CAG-repeat diseases. A small number of genetic and physical interactions have been described for Dmel\jp; see below and in the jp gene report.
[updated Jun. 2018 by FlyBase; FBrf0222196]
Junctional complexes between the plasma membrane (PM) and endoplasmic/sarcoplasmic reticulum (ER/SR) are a common feature of all excitable cell types and mediate cross talk between cell surface and intracellular ion channels. In muscle cells, junctophilin deficiency prevents junctional membrane complex formation and functional crosstalk between cell-surface Ca(2+) channels and ER/SR Ca(2+) release channels. (Takeshima et al. 2000, pubmed:10949023; Takeshima et al. 2015; pubmed:25659516).
Many to one: 4 human to 1 Drosophila. The human genes are JPH1, JPH2, JPH3, and JPH4.
Many to one: 4 human to 1 Drosophila. The human genes are JPH1, JPH2, JPH3, and JPH4.
Many to one: 4 human to 1 Drosophila. The human genes are JPH1, JPH2, JPH3, and JPH4.
Many to one: 4 human to 1 Drosophila. The human genes are JPH1, JPH2, JPH3, and JPH4.
Moderate-scoring ortholog of human JPH1, JPH2, JPH3, and JPH4 (1 Drosophila to 4 human). Dmel\jp shares 29-41% identity and 40-55% similarity with the human genes.
