{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTRPC2 is a member of the canonical transient receptor potential family whose activity is crucial for pheromone detection in many vertebrates. In species such as the mouse, TRPC2 is expressed exclusively in the vomeronasal organ (VNO) where it functions as the ion channel that transduces pheromonal signals, a role that appears to have been lost during primate evolution as the gene became a pseudogene in humans and Old World monkeys. This evolutionary inactivation is thought to coincide with a shift toward reliance on other sensory modalities, such as enhanced color vision, to convey social and reproductive cues."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in sensory transduction, TRPC2 is regulated at the molecular level through alternative splicing and calcium-dependent binding to calmodulin (CaM). Studies have demonstrated that among the TRPC family members, only specific splice variants of TRPC2 harbor an N-terminal CaM-binding domain that modulates the channel’s activity. This molecular heterogeneity, observed in tissues such as brain and testis, underpins the channel’s capacity to mediate agonist-stimulated and store-operated Ca2+ entry."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its pivotal role in pheromone signaling within the VNO, TRPC2 also contributes fundamentally to physiological processes such as sperm activation. In sperm cells, TRPC2 is activated upon contact with the oocyte’s zona pellucida, allowing Ca2+ entry that triggers the acrosome reaction, a necessary step for fertilization. Moreover, in the neuronal context of the VNO, activation of G protein-coupled receptors by pheromones leads to TRPC2-mediated depolarization, initiating neural signals that are relayed via the olfactory bulb to limbic and higher cortical centers, thereby influencing behaviors ranging from mating recognition to aggression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Emily R Liman, Hideki Innan "}, {"type": "b", "children": [{"type": "t", "text": "Relaxed selective pressure on an essential component of pheromone transduction in primate evolution."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0636123100"}], "href": "https://doi.org/10.1073/pnas.0636123100"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12631698"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12631698"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Eda Yildirim, Alexander Dietrich, Lutz Birnbaumer "}, {"type": "b", "children": [{"type": "t", "text": "The mouse C-type transient receptor potential 2 (TRPC2) channel: alternative splicing and calmodulin binding to its N terminus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0438036100"}], "href": "https://doi.org/10.1073/pnas.0438036100"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12601176"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12601176"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "E Yildirim, L Birnbaumer "}, {"type": "b", "children": [{"type": "t", "text": "TRPC2: molecular biology and functional importance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Handb Exp Pharmacol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/978-3-540-34891-7_3"}], "href": "https://doi.org/10.1007/978-3-540-34891-7_3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17217050"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17217050"}]}]}]}