Cyclic-Nucleotide- and HCN-Channel-Mediated Phototransduction in Intrinsically Photosensitive Retinal Ganglion Cells

被引：41

作者：

Jiang, Zheng ^{[1
,3
]}

Yue, Wendy W. S. ^{[1
,3
,4
,6
]}

Chen, Lujing ^{[1
,3
,5
]}

Sheng, Yanghui ^{[1
,3
,5
]}

Yau, King-Wai ^{[1
,2
,3
]}

机构：

[1] Johns Hopkins Univ, Solomon H Snyder Dept Neurosci, Sch Med, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Dept Ophthalmol, Sch Med, Baltimore, MD 21205 USA

[3] Johns Hopkins Univ, Ctr Sensory Biol, Sch Med, Baltimore, MD 21205 USA

[4] Johns Hopkins Univ, Sch Med, Biochem Cellular & Mol Biol Grad Program, Baltimore, MD 21205 USA

[5] Johns Hopkins Univ, Sch Med, Neurosci Grad Program, Baltimore, MD 21205 USA

[6] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94158 USA

来源：

CELL | 2018年 / 175卷 / 03期

关键词：

CGMP-GATED CHANNEL; CATION CURRENT; MICE LACKING; MELANOPSIN; PHOTORECEPTORS; EVOLUTION; LIGHT; EYE; ACTIVATION; PATHWAY;

D O I：

10.1016/j.cell.2018.08.055

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 PLC beta 4 (phospholipase C-beta 4) 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.

引用

页码：652 / +

页数：25

共 89 条

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