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Article ; Online: Coexistence within one cell of microvillous and ciliary phototransductions across M1- through M6-IpRGCs.

Li, Guang / Chen, Lujing / Jiang, Zheng / Yau, King-Wai

Proceedings of the National Academy of Sciences of the United States of America

2023 Volume 120, Issue 52, Page(s) e2315282120

Abstract: Intrinsically photosensitive retinal ganglion cells (ipRGCs) serve as primary photoceptors by expressing the photopigment, melanopsin, and also as retinal relay neurons for rod and cone signals en route to the brain, in both cases for the purpose of non- ... ...

Abstract	Intrinsically photosensitive retinal ganglion cells (ipRGCs) serve as primary photoceptors by expressing the photopigment, melanopsin, and also as retinal relay neurons for rod and cone signals en route to the brain, in both cases for the purpose of non-image vision as well as aspects of image vision. So far, six subtypes of ipRGCs (M1 through M6) have been characterized. Regarding their phototransduction mechanisms, we have previously found that, unconventionally, rhabdomeric (microvillous) and ciliary signaling motifs co-exist within a given M1-, M2-, and M4-ipRGC, with the first mechanism involving PLCβ4 and TRPC6,7 channels and the second involving cAMP and HCN channels. We have now examined M3-, M5-, and M6-cells and found that each cell likewise uses both signaling pathways for phototransduction, despite differences in the percentage representation by each pathway in a given ipRGC subtype for bright-flash responses (and saturated except for M6-cells). Generally, M3- and M5-cells show responses quite similar in kinetics to M2-responses, and M6-cell responses resemble broadly those of M1-cells although much lower in absolute sensitivity and amplitude. Therefore, similar to rod and cone subtypes in image vision, ipRGC subtypes possess the same phototransduction mechanism(s) even though they do not show microvilli or cilia morphologically.
MeSH term(s)	Vision, Ocular ; Light Signal Transduction/physiology ; Retinal Ganglion Cells/physiology ; Retinal Cone Photoreceptor Cells/metabolism ; Retinal Neurons/metabolism ; Rod Opsins/metabolism
Chemical Substances	Rod Opsins
Language	English
Publishing date	2023-12-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2315282120
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Article ; Online: Unusual phototransduction via cross-motif signaling from G

Chen, Lujing / Li, Guang / Jiang, Zheng / Yau, King-Wai

Proceedings of the National Academy of Sciences of the United States of America

2022 Volume 120, Issue 1, Page(s) e2216599120

Abstract: Nonimage-forming vision in mammals is mediated primarily by melanopsin (OPN4)-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs). In mouse M1-ipRGCs, melanopsin predominantly activates, via ... ...

Abstract	Nonimage-forming vision in mammals is mediated primarily by melanopsin (OPN4)-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs). In mouse M1-ipRGCs, melanopsin predominantly activates, via Gα
MeSH term(s)	Animals ; Mice ; Adenylyl Cyclases/genetics ; Adenylyl Cyclases/metabolism ; Light Signal Transduction/physiology ; Mammals/metabolism ; Nucleotides, Cyclic/metabolism ; Retinal Ganglion Cells/metabolism ; Retinal Ganglion Cells/physiology ; Rod Opsins/metabolism ; Signal Transduction/physiology ; GTP-Binding Protein alpha Subunits, Gq-G11/metabolism
Chemical Substances	Adenylyl Cyclases (EC 4.6.1.1) ; Nucleotides, Cyclic ; Rod Opsins ; GTP-Binding Protein alpha Subunits, Gq-G11 (EC 3.6.5.1)
Language	English
Publishing date	2022-12-29
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2216599120
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Article ; Online: Introducing Vadim Y. Arshavsky and Theodore G. Wensel, the 2013 recipients of the proctor medal.

Yau, King-Wai

Investigative ophthalmology & visual science

2013 Volume 54, Issue 12, Page(s) 7724

MeSH term(s)	Awards and Prizes ; History, 20th Century ; History, 21st Century ; Humans ; Ophthalmology/history ; Societies, Medical ; United States
Language	English
Publishing date	2013-11-21
Publishing country	United States
Document type	Biography ; Historical Article
ZDB-ID	391794-0
ISSN	1552-5783 ; 0146-0404
ISSN (online)	1552-5783
ISSN	0146-0404
DOI	10.1167/iovs.13-11778
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Article ; Online: Molecular determinants of response kinetics of mouse M1 intrinsically-photosensitive retinal ganglion cells

Yanghui Sheng / Lujing Chen / Xiaozhi Ren / Zheng Jiang / King-Wai Yau

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 18

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, ... ...

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 (τ1 and τ2) 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, τ3, 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.
Keywords	Medicine ; R ; Science ; Q
Subject code	612
Language	English
Publishing date	2021-12-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Molecular determinants of response kinetics of mouse M1 intrinsically-photosensitive retinal ganglion cells.

Sheng, Yanghui / Chen, Lujing / Ren, Xiaozhi / Jiang, Zheng / Yau, King-Wai

Scientific reports

2021 Volume 11, Issue 1, Page(s) 23424

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 ... ...

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
MeSH term(s)	Animals ; Circadian Rhythm/physiology ; Dependovirus ; Intravitreal Injections ; Kinetics ; Light ; Light Signal Transduction ; Mice ; Mice, Transgenic ; Mutation ; Neurosciences ; Phosphorylation ; Retinal Cone Photoreceptor Cells/metabolism ; Retinal Ganglion Cells/metabolism ; Rod Opsins/chemistry ; Signal Transduction ; Vision, Ocular ; beta-Arrestins/chemistry
Chemical Substances	Rod Opsins ; beta-Arrestins ; melanopsin
Language	English
Publishing date	2021-12-06
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-02832-9
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Introducing Marie E. Burns, the 2009 Recipient of the Cogan Award.

Yau, King-Wai

Investigative ophthalmology & visual science

2010 Volume 51, Issue 3, Page(s) 1282

MeSH term(s)	Awards and Prizes ; California ; Florida ; History, 20th Century ; History, 21st Century ; Humans ; Ophthalmology/history ; Societies, Scientific
Language	English
Publishing date	2010-03
Publishing country	United States
Document type	Biography ; Historical Article ; Journal Article
ZDB-ID	391794-0
ISSN	1552-5783 ; 0146-0404
ISSN (online)	1552-5783
ISSN	0146-0404
DOI	10.1167/iovs.09-4479
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Zs.A 45: Show issues

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Article ; Online: Low signaling efficiency from receptor to effector in olfactory transduction: A quantified ligand-triggered GPCR pathway.

Li, Rong-Chang / Molday, Laurie L / Lin, Chih-Chun / Ren, Xiaozhi / Fleischmann, Alexander / Molday, Robert S / Yau, King-Wai

Proceedings of the National Academy of Sciences of the United States of America

2022 Volume 119, Issue 32, Page(s) e2121225119

Abstract: G protein-coupled receptor (GPCR) signaling is ubiquitous. As an archetype of this signaling motif, rod phototransduction has provided many fundamental, quantitative details, including a dogma that one active GPCR molecule activates a substantial number ... ...

Abstract	G protein-coupled receptor (GPCR) signaling is ubiquitous. As an archetype of this signaling motif, rod phototransduction has provided many fundamental, quantitative details, including a dogma that one active GPCR molecule activates a substantial number of downstream G protein/enzyme effector complexes. However, rod phototransduction is light-activated, whereas GPCR pathways are predominantly ligand-activated. Here, we report a detailed study of the ligand-triggered GPCR pathway in mammalian olfactory transduction, finding that an odorant-receptor molecule when (one-time) complexed with its most effective odorants produces on average much less than one downstream effector. Further experiments gave a nominal success probability of tentatively ∼10
MeSH term(s)	Animals ; Ligands ; Light Signal Transduction ; Mammals/metabolism ; Odorants ; Receptors, G-Protein-Coupled/metabolism ; Receptors, Odorant/metabolism ; Retinal Rod Photoreceptor Cells ; Signal Transduction ; Smell
Chemical Substances	Ligands ; Receptors, G-Protein-Coupled ; Receptors, Odorant
Language	English
Publishing date	2022-08-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2121225119
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Light-dependent photoreceptor orientation in mouse retina.

Chai, Zuying / Silverman, Daniel / Li, Guang / Williams, David / Raviola, Elio / Yau, King-Wai

Science advances

2020 Volume 6, Issue 51

Abstract: Almost a century ago, Stiles and Crawford reported that the human eye is more sensitive to light entering through the pupil center than through its periphery (Stiles-Crawford effect). This psychophysical phenomenon, later found to correlate with ... ...

Abstract	Almost a century ago, Stiles and Crawford reported that the human eye is more sensitive to light entering through the pupil center than through its periphery (Stiles-Crawford effect). This psychophysical phenomenon, later found to correlate with photoreceptor orientation toward the pupil, was dynamically phototropic, adjustable within days to an eccentrically displaced pupil. For decades, this phototropism has been speculated to involve coordinated movements of the rectilinear photoreceptor outer and inner segments. We report here that, unexpectedly, the murine photoreceptor outer segment has a seemingly light-independent orientation, but the inner segment's orientation undergoes light-dependent movement, giving rise to nonrectilinear outer and inner segments in adult mice born and reared in darkness. Light during an early critical period (~P0 to P8), however, largely sets the correct photoreceptor orientation permanently afterward. Unexpectedly, abolishing rod and cone phototransductions did not mimic darkness in early life, suggesting photosignaling extrinsic to rods and cones is involved.
Language	English
Publishing date	2020-12-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.abe2782
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Cyclic-Nucleotide- and HCN-Channel-Mediated Phototransduction in Intrinsically Photosensitive Retinal Ganglion Cells.

Jiang, Zheng / Yue, Wendy W S / Chen, Lujing / Sheng, Yanghui / Yau, King-Wai

Cell

2018 Volume 175, Issue 3, Page(s) 652–664.e12

Abstract: Non-image-forming vision in mammals is mediated primarily by melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs). In mouse M1-ipRGCs, by far the best-studied subtype, melanopsin activates PLCβ4 (phospholipase C-β4) to open ...

Abstract	Non-image-forming vision in mammals is mediated primarily by melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs). In mouse M1-ipRGCs, by far the best-studied subtype, melanopsin activates PLCβ4 (phospholipase C-β4) to open TRPC6,7 channels, mechanistically similar to phototransduction in fly rhabdomeric (microvillous) photoreceptors. We report here that, surprisingly, mouse M4-ipRGCs rely on a different and hitherto undescribed melanopsin-driven, ciliary phototransduction mechanism involving cyclic nucleotide as the second messenger and HCN channels rather than CNG channels as the ion channel for phototransduction. Even more surprisingly, within an individual mouse M2-ipRGC, this HCN-channel-dependent, ciliary phototransduction pathway operates in parallel with the TRPC6,7-dependent rhabdomeric pathway. These findings reveal a complex heterogeneity in phototransduction among ipRGCs and, more importantly, break a general dogma about segregation of the two phototransduction motifs, likely with strong evolutionary implications.
MeSH term(s)	Animals ; Cyclic Nucleotide-Gated Cation Channels/metabolism ; Female ; HEK293 Cells ; Humans ; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Nucleotides, Cyclic/metabolism ; Retinal Ganglion Cells/metabolism ; Retinal Ganglion Cells/physiology ; TRPC Cation Channels/metabolism ; Vision, Ocular
Chemical Substances	Cyclic Nucleotide-Gated Cation Channels ; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels ; Nucleotides, Cyclic ; TRPC Cation Channels
Language	English
Publishing date	2018-09-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2018.08.055
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Zs.A 1167: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Cyclic-Nucleotide- and HCN-Channel-Mediated Phototransduction in Intrinsically Photosensitive Retinal Ganglion Cells

Jiang, Zheng / Yue, Wendy W.S / Chen, Lujing / Sheng, Yanghui / Yau, King-Wai

Cell. 2018 Oct. 18, v. 175, no. 3

2018

Abstract	Non-image-forming vision in mammals is mediated primarily by melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs). In mouse M1-ipRGCs, by far the best-studied subtype, melanopsin activates PLCβ4 (phospholipase C-β4) to open TRPC6,7 channels, mechanistically similar to phototransduction in fly rhabdomeric (microvillous) photoreceptors. We report here that, surprisingly, mouse M4-ipRGCs rely on a different and hitherto undescribed melanopsin-driven, ciliary phototransduction mechanism involving cyclic nucleotide as the second messenger and HCN channels rather than CNG channels as the ion channel for phototransduction. Even more surprisingly, within an individual mouse M2-ipRGC, this HCN-channel-dependent, ciliary phototransduction pathway operates in parallel with the TRPC6,7-dependent rhabdomeric pathway. These findings reveal a complex heterogeneity in phototransduction among ipRGCs and, more importantly, break a general dogma about segregation of the two phototransduction motifs, likely with strong evolutionary implications.
Keywords	ganglia ; hydrogen cyanide ; ion channels ; mice ; phospholipase C ; photoreceptors ; photosensitivity ; phototransduction ; second messengers ; vision
Language	English
Dates of publication	2018-1018
Size	p. 652-664.e12.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2018.08.055
Database	NAL-Catalogue (AGRICOLA)

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