PDF(468 KB)
Research progress in cyclic nucleotide-gated ion channels and its function
Lin FNAG,Shipeng LI
PDF(468 KB)
PDF(468 KB)
Research progress in cyclic nucleotide-gated ion channels and its function
)Cyclic nucleotide-gated （CNG） ion channel is a type of non-selective tetrameric cation channel that can be directly activated by intracellular signaling molecules—cyclic nucleotides， and is one of the main pathways for calcium ions to enter the cells. The CNG channel proteins are encoded by six different genes： four A subunits and two B subunits. The activity of CNG ion channel can be modulated by calcium/calmodulin （Ca2+/CaM） as well as phosphorylation or the action of phosphatidylinositol on the membrane， thereby altering intracellular calcium ion concentrations and participating in the regulation of a variety of biological functions. Since the discovery of CNG ion channels in rod photoreceptors， it has undergone research processes such as physiological functions， cloning related genes， understanding regulatory mechanisms， analyzing crystal structures， and developing related gene therapy methods. They play an important role in signal transduction in olfactory sensory neurons （OSNs）of vision and smell. This article briefly reviews the function， structure， regulatory mechanism， and relationship with related diseases of CNG ion channel， in order to provide the theoretical basis and reference for the treatment of CNG ion channel-related diseases.
Cyclic nucleotide-gated ion channel / Calcium ion / Regulatory mechanism / Retina
R-33
| 1 | FESENKO E E， KOLESNIKOV S S， LYUBARSKY A L. Induction by cyclic GMP of cationic conductance in plasma membrane of retinal rod outer segment［J］. Nature， 1985， 313（6000）： 310-313. |
| 2 | NAKAMURA T， GOLD G H. A cyclic nucleotide-gated conductance in olfactory receptor cilia［J］. Nature， 1987， 325（6103）： 442-444. |
| 3 | BURNS M E， ARSHAVSKY V Y. Beyond counting photons： trials and trends in vertebrate visual transduction［J］. Neuron， 2005， 48（3）： 387-401. |
| 4 | HSU Y T， MOLDAY R S. Modulation of the cGMP-gated channel of rod photoreceptor cells by calmodulin［J］. Nature， 1993， 361（6407）： 76-79. |
| 5 | SAVCHENKO A， BARNES S， KRAMER R H. Cyclic-nucleotide-gated channels mediate synaptic feedback by nitric oxide［J］. Nature， 1997， 390（6661）： 694-698. |
| 6 | FRINGS S. Chemoelectrical signal transduction in olfactory sensory neurons of air-breathing vertebrates［J］. Cell Mol Life Sci， 2001， 58（4）： 510-519. |
| 7 | TOGASHI K， VON SCHIMMELMANN M J， NISHIYAMA M， et al. Cyclic GMP-gated CNG channels function in Sema3A-induced growth cone repulsion［J］. Neuron， 2008， 58（5）： 694-707. |
| 8 | HEINE S， MICHALAKIS S， KALLENBORN-GERHARDT W， et al. CNGA3： a target of spinal nitric oxide/cGMP signaling and modulator of inflammatory pain hypersensitivity［J］. J Neurosci， 2011， 31（31）： 11184-11192. |
| 9 | KALLENBORN-GERHARDT W， METZNER K， LU R R， et al. Neuropathic and cAMP-induced pain behavior is ameliorated in mice lacking CNGB1［J］. Neuropharmacology， 2020， 171： 108087. |
| 10 | MICHALAKIS S， KLEPPISCH T， POLTA S A，et al. Altered synaptic plasticity and behavioral abnormalities in CNGA3-deficient mice［J］. Genes Brain Behav， 2011， 10（2）： 137-148. |
| 11 | BRADLEY J， REUTER D， FRINGS S. Facilitation of calmodulin-mediated odor adaptation by cAMP-gated channel subunits［J］. Science， 2001， 294（5549）： 2176-2178. |
| 12 | KAUPP U B， NIIDOME T， TANABE T， et al. Primary structure and functional expression from complementary DNA of the rod photoreceptor cyclic GMP-gated channel［J］. Nature， 1989， 342（6251）： 762-766. |
| 13 | GERSTNER A， ZONG X， HOFMANN F， et al. Molecular cloning and functional characterization of a new modulatory cyclic nucleotide-gated channel subunit from mouse retina［J］. J Neurosci， 2000， 20（4）：1324-1332. |
| 14 | COBURN C M， BARGMANN C I. A putative cyclic nucleotide-gated channel is required for sensory development and function in C. elegans［J］. Neuron， 1996， 17（4）： 695-706. |
| 15 | BAUMANN A， FRINGS S， GODDE M， et al. Primary structure and functional expression of a Drosophila cyclic nucleotide-gated channel present in eyes and antennae［J］. EMBO J， 1994， 13（21）： 5040-5050. |
| 16 | MIYAZU M， TANIMURA T， SOKABE M. Molecular cloning and characterization of a putative cyclic nucleotide-gated channel from Drosophila melanogaster［J］. Insect Mol Biol， 2000，9（3）： 283-292. |
| 17 | ZHONG H N， MOLDAY L L， MOLDAY R S， et al. The heteromeric cyclic nucleotide-gated channel adopts a 3A： 1B stoichiometry［J］. Nature， 2002， 420（6912）： 193-198. |
| 18 | PENG C H， RICH E D， VARNUM M D. Subunit configuration of heteromeric cone cyclic nucleotide-gated channels［J］. Neuron， 2004， 42（3）： 401-410. |
| 19 | ZHENG J， ZAGOTTA W N. Stoichiometry and assembly of olfactory cyclic nucleotide-gated channels［J］. Neuron， 2004， 42（3）： 411-421. |
| 20 | RITTER L M， KHATTREE N， TAM B， et al. In situ visualization of protein interactions in sensory neurons： glutamic acid-rich proteins （GARPs） play differential roles for photoreceptor outer segment scaffolding［J］. J Neurosci， 2011， 31（31）： 11231-11243. |
| 21 | SU Y， DOSTMANN W R， HERBERG F W， et al. Regulatory subunit of protein kinase A： structure of deletion mutant with cAMP binding domains［J］. Science， 1995， 269（5225）： 807-813. |
| 22 | VARNUM M D， BLACK K D， ZAGOTTA W N. Molecular mechanism for ligand discrimination of cyclic nucleotide-gated channels［J］. Neuron， 1995， 15（3）： 619-625. |
| 23 | ALTENHOFEN W， LUDWIG J， EISMANN E，et al. Control of ligand specificity in cyclic nucleotide-gated channels from rod photoreceptors and olfactory epithelium［J］.Proc Natl Acad Sci U S A，1991，88（21）： 9868-9872. |
| 24 | GORDON S E， DOWNING-PARK J， ZIMMERMAN A L.Modulation of the cGMP-gated ion channel in frog rods by calmodulin and an endogenous inhibitory factor［J］. J Physiol， 1995， 486（Pt 3）： 533-546. |
| 25 | GORDON S E， DOWNING-PARK J， TAM B， et al. Diacylglycerol analogs inhibit the rod cGMP-gated channel by a phosphorylation-independent mechanism［J］. Biophys J， 1995， 69（2）： 409-417. |
| 26 | EVANS E G B， MORGAN J L W， DIMAIO F， et al. Allosteric conformational change of a cyclic nucleotide-gated ion channel revealed by DEER spectroscopy［J］. Proc Natl Acad Sci U S A，2020，117（20）：10839-10847. |
| 27 | LIU M， CHEN T Y， AHAMED B， et al. Calcium-calmodulin modulation of the olfactory cyclic nucleotide-gated cation channel［J］. Science， 1994， 266（5189）： 1348-1354. |
| 28 | VARNUM M D， ZAGOTTA W N. Interdomain interactions underlying activation of cyclic nucleotide-gated channels［J］. Science， 1997， 278（5335）： 110-113. |
| 29 | TRUDEAU M C， ZAGOTTA W N. Mechanism of calcium/calmodulin inhibition of rod cyclic nucleotide-gated channels［J］. Proc Natl Acad Sci U S A， 2002，99（12）： 8424-8429. |
| 30 | MALLOUK N， ILDEFONSE M， PAGèS F， et al. Basis for intracellular retention of a human mutant of the retinal rod channel alpha subunit［J］. J Membr Biol， 2002， 185（2）： 129-136. |
| 31 | FLYNN G E， BLACK K D， ISLAS L D， et al. Structure and rearrangements in the carboxy-terminal region of SpIH channels［J］.Structure，2007，15（6）：671-682. |
| 32 | FLYNN G E， ZAGOTTA W N. Conformational changes in S6 coupled to the opening of cyclic nucleotide-gated channels［J］. Neuron， 2001， 30（3）： 689-698. |
| 33 | TIBBS G R， GOULDING E H， SIEGELBAUM S A. Allosteric activation and tuning of ligand efficacy in cyclic-nucleotide-gated channels［J］. Nature，1997，386（6625）： 612-615. |
| 34 | CRAVEN K B， ZAGOTTA W N. CNG and HCN channels： two peas， one pod［J］. Annu Rev Physiol， 2006， 68： 375-401. |
| 35 | XUE J， HAN Y， ZENG W Z， et al. Structural mechanisms of gating and selectivity of human rod CNGA1 channel［J］.Neuron，2021，109（8）：1302-1313. |
| 36 | SONG Y J， CYGNAR K D， SAGDULLAEV B， et al. Olfactory CNG channel desensitization by Ca2+/CaM via the B1b subunit affects response termination but not sensitivity to recurring stimulation［J］.Neuron，2008，58（3）： 374-386. |
| 37 | NACHE V， WONGSAMITKUL N， KUSCH J， et al. Deciphering the function of the CNGB1b subunit in olfactory CNG channels［J］. Sci Rep， 2016， 6： 29378. |
| 38 | REBRIK T I， KORENBROT J I. In intact mammalian photoreceptors， Ca2+-dependent modulation of cGMP-gated ion channels is detectable in cones but not in rods［J］. J Gen Physiol， 2004， 123（1）： 63-75. |
| 39 | MOLOKANOVA E， KRAJEWSKI J L， SATPAEV D， et al. Subunit contributions to phosphorylation-dependent modulation of bovine rod cyclic nucleotide-gated channels［J］.J Physiol， 2003， 552（Pt 2）： 345-356. |
| 40 | MüLLER F， VANTLER M， WEITZ D， et al. Ligand sensitivity of the 2 subunit from the bovine cone cGMP-gated channel is modulated by protein kinase C but not by calmodulin［J］. J Physiol， 2001， 532（Pt 2）： 399-409. |
| 41 | WOMACK K B， GORDON S E， HE F， et al. Do phosphatidylinositides modulate vertebrate phototransduction？［J］. J Neurosci， 2000， 20（8）： 2792-2799. |
| 42 | BRIGHT S R， RICH E D， VARNUM M D. Regulation of human cone cyclic nucleotide-gated channels by endogenous phospholipids and exogenously applied phosphatidylinositol 3， 4， 5-trisphosphate［J］. Mol Pharmacol， 2007， 71（1）： 176-183. |
| 43 | ZHAINAZAROV A B， SPEHR M， WETZEL C H， et al. Modulation of the olfactory CNG channel by Ptdlns（3， 4， 5）P3［J］. J Membr Biol， 2004， 201（1）： 51-57. |
| 44 | CHEN S K， KO G Y P， DRYER S E. Somatostatin peptides produce multiple effects on gating properties of native cone photoreceptor cGMP-gated channels that depend on circadian phase and previous illumination［J］. J Neurosci， 2007， 27（45）： 12168-12175. |
| 45 | KO G Y P， KO M L， DRYER S E. Circadian phase-dependent modulation of cGMP-gated channels of cone photoreceptors by dopamine and D2 agonist［J］. J Neurosci， 2003， 23（8）： 3145-3153. |
| 46 | KO G Y P， KO M L， DRYER S E. Circadian regulation of cGMP-gated channels of vertebrate cone photoreceptors： role of cAMP and Ras［J］. J Neurosci， 2004， 24（6）： 1296-1304. |
| 47 | GUPTA V K， RAJALA A， DALY R J， et al. Growth factor receptor-bound protein 14： a new modulator of photoreceptor-specific cyclic-nucleotide-gated channel［J］. EMBO Rep， 2010， 11（11）： 861-867. |
| 48 | GUPTA V K， RAJALA A， RAJALA R V. Insulin receptor regulates photoreceptor CNG channel activity［J］. Am J Physiol Endocrinol Metab， 2012，303（11）： E1363-E1372. |
| 49 | RAJALA R V， MCCLELLAN M E， ASH J D， et al. In vivo regulation of phosphoinositide 3-kinase in retina through light-induced tyrosine phosphorylation of the insulin receptor beta-subunit［J］. J Biol Chem， 2002， 277（45）： 43319-43326. |
| 50 | LI G Y， RAJALA A， WIECHMANN A F， et al. Activation and membrane binding of retinal protein kinase Balpha/Akt1 is regulated through light-dependent generation of phosphoinositides［J］. J Neurochem， 2008， 107（5）： 1382-1397. |
| 51 | PAQUET-DURAND F， BECK S， MICHALAKIS S， et al. A key role for cyclic nucleotide gated （CNG） channels in cGMP-related retinitis pigmentosa［J］. Hum Mol Genet， 2011， 20（5）： 941-947. |
| 52 | WANG L， ZOU T D， LIN Y Q， et al. Identification of a novel homozygous variant in the CNGA1 gene in a Chinese family with autosomal recessive retinitis pigmentosa［J］. Mol Med Rep， 2020， 22（3）： 2516-2520. |
| 53 | XUE J， HAN Y， ZENG W Z， et al. Structural mechanisms of assembly， permeation， gating， and pharmacology of native human rod CNG channel［J］. Neuron， 2022， 110（1）： 86-95.e5. |
| 54 | PETERSEN-JONES S M， OCCELLI L M， WINKLER P A， et al. Patients and animal models of CNGβ1-deficient retinitis pigmentosa support gene augmentation approach［J］. J Clin Invest， 2018，128（1）： 190-206. |
| 55 | MICHAELIDES M， ALIGIANIS I A， AINSWORTH J R，et al. Progressive cone dystrophy associated with mutation in CNGB3［J］. Invest Ophthalmol Vis Sci， 2004， 45（6）： 1975-1982. |
| 56 | ZHENG X， HU Z， LI H， et al. Structure of the human cone photoreceptor cyclic nucleotide-gated channel［J］. Nat Struct Mol Biol， 2022， 29（1）： 40-46. |
| 57 | ZHENG X D， LI H， HU Z S， et al. Structural and functional characterization of an achromatopsia-associated mutation in a phototransduction channel［J］. Commun Biol， 2022， 5（1）： 190. |
| 58 | KARSTENSEN H G， MANG Y， FARK T， et al. The first mutation in CNGA2 in two brothers with anosmia［J］. Clin Genet， 2015， 88（3）： 293-296. |
| 59 | SAILANI M R， JINGGA I， MIRMAZLOMI S H，et al. Isolated congenital anosmia and CNGA2 mutation［J］. Sci Rep， 2017， 7（1）： 2667. |
/
| 〈 |
|
〉 |
AI Summary
