{"doi":"10.1038/s41598-021-02832-9","title":"Molecular determinants of response kinetics of mouse M1 intrinsically-photosensitive retinal ganglion cells","abstract":"Abstract Intrinsically-photosensitive retinal ganglion cells (ipRGCs) are non-rod/non-cone retinal photoreceptors expressing the visual pigment, melanopsin, to detect ambient irradiance for various non-image-forming visual functions. The M1-subtype, amongst the best studied, mediates primarily circadian photoentrainment and pupillary light reflex. Their intrinsic light responses are more prolonged than those of rods and cones even at the single-photon level, in accordance with the typically slower time course of non-image-forming vision. The short (OPN4S) and long (OPN4L) alternatively-spliced forms of melanopsin proteins are both present in M1-ipRGCs, but their functional difference is unclear. We have examined this point by genetically removing the Opn4 gene ( Opn4 −/− ) in mouse and re-expressing either OPN4S or OPN4L singly in Opn4 −/− mice by using adeno-associated virus, but found no obvious difference in their intrinsic dim-flash responses. Previous studies have indicated that two dominant slow steps in M1-ipRGC phototransduction dictate these cells’ intrinsic dim-flash-response kinetics, with time constants (τ 1 and τ 2 ) at room temperature of ~ 2 s and ~ 20 s, respectively. Here we found that melanopsin inactivation by phosphorylation or by β-arrestins may not be one of these two steps, because their genetic disruptions did not prolong the two time constants or affect the response waveform. Disruption of GAP (GTPase-Activating-Protein) activity on the effector enzyme, PLCβ4, in M1-ipRGC phototransduction to slow down G-protein deactivation also did not prolong the response decay, but caused its rising phase to become slightly sigmoidal by giving rise to a third time constant, τ 3 , of ~ 2 s (room temperature). This last observation suggests that GAP-mediated G-protein deactivation does partake in the flash-response termination, although normally with a time constant too short to be visible in the response waveform.","journal":"Scientific Reports","year":2021,"id":204746,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9601,"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":787167,"name":"Lujing Chen","orcid":"0009-0003-1614-966X","position":1,"is_corresponding":false},{"id":344008,"name":"Xiaozhi Ren","orcid":"0009-0009-4334-1124","position":2,"is_corresponding":false},{"id":88567,"name":"Zheng Jiang","orcid":"0000-0003-4297-464X","position":3,"is_corresponding":false},{"id":443632,"name":"King‐Wai Yau","orcid":"0000-0001-8880-3091","position":4,"is_corresponding":false},{"id":787166,"name":"Yanghui Sheng","orcid":"0000-0002-4204-1965","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":null,"created_at":"2026-07-18T23:51:26.121843Z","pmid":"34873237","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":[]}