{"doi":"10.1093/genetics/iyab063","title":"<i>Caenorhabditis elegans</i> junctophilin has tissue-specific functions and regulates neurotransmission with extended-synaptotagmin","abstract":"The junctophilin family of proteins tether together plasma membrane (PM) and endoplasmic reticulum (ER) membranes, and couple PM- and ER-localized calcium channels. Understanding in vivo functions of junctophilins is of great interest for dissecting the physiological roles of ER-PM contact sites. Here, we show that the sole Caenorhabditis elegans junctophilin JPH-1 localizes to discrete membrane contact sites in neurons and muscles and has important tissue-specific functions. jph-1 null mutants display slow growth and development due to weaker contraction of pharyngeal muscles, leading to reduced feeding. In the body wall muscle, JPH-1 colocalizes with the PM-localized EGL-19 voltage-gated calcium channel and ER-localized UNC-68 RyR calcium channel, and is required for animal movement. In neurons, JPH-1 colocalizes with the membrane contact site protein Extended-SYnaptoTagmin 2 (ESYT-2) in the soma, and is present near presynaptic release sites. Interestingly, jph-1 and esyt-2 null mutants display mutual suppression in their response to aldicarb, suggesting that JPH-1 and ESYT-2 have antagonistic roles in neuromuscular synaptic transmission. Additionally, we find an unexpected cell nonautonomous effect of jph-1 in axon regrowth after injury. Genetic double mutant analysis suggests that jph-1 functions in overlapping pathways with two PM-localized voltage-gated calcium channels, egl-19 and unc-2, and with unc-68 for animal health and development. Finally, we show that jph-1 regulates the colocalization of EGL-19 and UNC-68 and that unc-68 is required for JPH-1 localization to ER-PM puncta. Our data demonstrate important roles for junctophilin in cellular physiology, and also provide insights into how junctophilin functions together with other calcium channels in vivo.","journal":"Genetics","year":2021,"id":181961,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9526,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":586363,"name":"Zilu Wu","orcid":null,"position":1,"is_corresponding":false},{"id":585693,"name":"Stephen Nurrish","orcid":"0000-0002-2653-9384","position":2,"is_corresponding":false},{"id":281680,"name":"Suhong Xu","orcid":"0000-0002-4079-340X","position":3,"is_corresponding":false},{"id":585694,"name":"Joshua M. Kaplan","orcid":"0000-0001-7418-7179","position":4,"is_corresponding":false},{"id":281679,"name":"Andrew Chisholm","orcid":"0000-0001-5091-0537","position":5,"is_corresponding":false},{"id":335049,"name":"Yishi Jin","orcid":"0000-0002-9371-9860","position":6,"is_corresponding":false},{"id":585692,"name":"Christopher Piggott","orcid":"0000-0002-3492-2105","position":0,"is_corresponding":true}],"reference_count":74,"raw_metadata":null,"created_at":"2026-07-18T23:48:09.223560Z","pmid":"33871019","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}