{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nVoltage-sensing domains (VSDs) are found in a wide variety of membrane proteins—from canonical ion channels that mediate rapid electrical signaling to non‐conducting proteins that regulate specialized cellular processes. Although classic voltage‐gated channels possess both a VSD and a pore domain, several proteins contain VSDs without an associated ion pore, indicating roles beyond immediate excitability"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n\n<br><br>\nOne example is HVRP1, a protein related to the Hv1 channel, which is expressed predominantly in the central nervous system. In the cerebellum, HVRP1 is localized in granule neurons at the postsynaptic side of glutamatergic synapses. Despite sharing sequence and structural similarities with Hv1, HVRP1 does not contribute to classical electrical excitability but instead appears to play a specialized role in neuronal signaling and synaptic function"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n\n<br><br>\nIn a related vein, hTMEM266 is predicted to contain an S1–S4 voltage‐sensing domain along with partially structured cytoplasmic termini. Experimental findings show that hTMEM266 forms oligomers and undergoes both rapid (microsecond) and slower (millisecond) conformational rearrangements in response to voltage changes. Moreover, a Zn²⁺ binding site within the protein modulates its slower transition, underscoring its role as a bona fide voltage sensor. This rapid responsiveness may be exploited in the design of new genetically encoded voltage indicators, highlighting a potential regulatory function in cellular processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Iris H Kim, Peter Hevezi, Csaba Varga, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Evidence for functional diversity between the voltage-gated proton channel Hv1 and its closest related protein HVRP1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0105926"}], "href": "https://doi.org/10.1371/journal.pone.0105926"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25165868"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25165868"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Ferenc Papp, Suvendu Lomash, Orsolya Szilagyi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TMEM266 is a functional voltage sensor regulated by extracellular Zn"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "2"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": "."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.42372"}], "href": "https://doi.org/10.7554/eLife.42372"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30810529"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30810529"}]}]}]}