دورية أكاديمية
The GARP Domain of the Rod CNG Channel's β1-Subunit Contains Distinct Sites for Outer Segment Targeting and Connecting to the Photoreceptor Disk Rim.
العنوان: | The GARP Domain of the Rod CNG Channel's β1-Subunit Contains Distinct Sites for Outer Segment Targeting and Connecting to the Photoreceptor Disk Rim. |
---|---|
المؤلفون: | Pearring JN; Department of Ophthalmology, University of Michigan, Ann Arbor, Michigan 48105 pearring@umich.edu.; Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48105., Martínez-Márquez J; Department of Ophthalmology, University of Michigan, Ann Arbor, Michigan 48105.; Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48105., Willer JR; Department of Ophthalmology, University of Michigan, Ann Arbor, Michigan 48105.; Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48105., Lieu EC; Albert Eye Research Institute, Duke University, Durham, North Carolina 27710., Salinas RY; Albert Eye Research Institute, Duke University, Durham, North Carolina 27710., Arshavsky VY; Albert Eye Research Institute, Duke University, Durham, North Carolina 27710. |
المصدر: | The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2021 Apr 07; Vol. 41 (14), pp. 3094-3104. Date of Electronic Publication: 2021 Feb 26. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Society for Neuroscience Country of Publication: United States NLM ID: 8102140 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1529-2401 (Electronic) Linking ISSN: 02706474 NLM ISO Abbreviation: J Neurosci Subsets: MEDLINE |
أسماء مطبوعة: | Publication: Washington, DC : Society for Neuroscience Original Publication: [Baltimore, Md.] : The Society, c1981- |
مواضيع طبية MeSH: | Cyclic Nucleotide-Gated Cation Channels/*genetics , Cyclic Nucleotide-Gated Cation Channels/*metabolism , Membrane Proteins/*genetics , Membrane Proteins/*metabolism , Nerve Tissue Proteins/*genetics , Nerve Tissue Proteins/*metabolism , Protein Domains/*physiology , Rod Cell Outer Segment/*metabolism, Animals ; Animals, Genetically Modified ; Animals, Newborn ; Binding Sites/physiology ; Cyclic Nucleotide-Gated Cation Channels/chemistry ; Female ; Male ; Membrane Proteins/chemistry ; Mice ; Mice, Knockout ; Mice, Transgenic ; Nerve Tissue Proteins/chemistry ; Rod Cell Outer Segment/chemistry ; Xenopus |
مستخلص: | Vision begins when light is captured by the outer segment organelle of photoreceptor cells in the retina. Outer segments are modified cilia filled with hundreds of flattened disk-shaped membranes. Disk membranes are separated from the surrounding plasma membrane, and each membrane type has unique protein components. The mechanisms underlying this protein sorting remain entirely unknown. In this study, we investigated the outer segment delivery of the rod cyclic nucleotide-gated (CNG) channel, which is located in the outer segment plasma membrane, where it mediates the electrical response to light. Using Xenopus and mouse models of both sexes, we now show that the targeted delivery of the CNG channel to the outer segment uses the conventional secretory pathway, including protein processing in both ER and Golgi, and requires preassembly of its constituent α1 and β1 subunits. We further demonstrate that the N-terminal glutamic acid-rich protein (GARP) domain of CNGβ1 contains two distinct functional regions. The glutamic acid-rich region encodes specific information targeting the channel to rod outer segments. The adjacent proline-enriched region connects the CNG channel to photoreceptor disk rims, likely through an interaction with peripherin-2. These data reveal fine functional specializations within the structural domains of the CNG channel and suggest that its sequestration to the outer segment plasma membrane requires an interaction with peripherin-2. SIGNIFICANCE STATEMENT Neurons and other differentiated cells have a remarkable ability to deliver and organize signaling proteins at precise subcellular locations. We now report that the CNG channel, mediating the electrical response to light in rod photoreceptors, contains two specialized regions within the N terminus of its β-subunit: one responsible for delivery of this channel to the ciliary outer segment organelle and another for subsequent channel sequestration into the outer segment plasma membrane. These findings expand our understanding of the molecular specializations used by neurons to populate their critical functional compartments. (Copyright © 2021 the authors.) |
References: | J Biol Chem. 2017 May 12;292(19):7850-7865. (PMID: 28325841) J Neurosci. 2014 Jan 15;34(3):992-1006. (PMID: 24431457) J Biol Chem. 2004 Nov 19;279(47):49010-8. (PMID: 15347652) J Physiol. 1988 Jul;401:309-27. (PMID: 2845062) J Cell Biol. 1978 Aug;78(2):415-25. (PMID: 690173) FEBS Lett. 1996 Jul 1;389(2):213-8. (PMID: 8766832) J Cell Biol. 2000 Dec 25;151(7):1369-80. (PMID: 11134067) J Neurosci. 2019 May 1;39(18):3376-3393. (PMID: 30819798) J Neurosci. 2005 Jan 5;25(1):130-8. (PMID: 15634774) Gene. 2000 Mar 21;245(2):311-8. (PMID: 10717482) PLoS One. 2015 Sep 25;10(9):e0138508. (PMID: 26406599) Nature. 2002 Nov 14;420(6912):193-8. (PMID: 12432397) Development. 1996 Oct;122(10):3173-83. (PMID: 8898230) J Cell Biol. 1991 Jun;113(6):1281-93. (PMID: 1828467) PLoS One. 2013;8(1):e54292. (PMID: 23342122) J Cell Sci. 2009 Apr 15;122(Pt 8):1192-200. (PMID: 19339551) Nature. 1993 Apr 22;362(6422):764-7. (PMID: 7682292) Mol Biol Cell. 2004 Apr;15(4):2027-37. (PMID: 14767063) Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10620-5. (PMID: 9724753) Biochemistry. 1990 May 15;29(19):4691-8. (PMID: 2372552) Hum Mol Genet. 2019 Feb 1;28(3):459-475. (PMID: 30307502) Curr Biol. 2006 Jun 20;16(12):1211-6. (PMID: 16782012) Adv Exp Med Biol. 2010;664:63-70. (PMID: 20238003) Ophthalmic Genet. 2009 Sep;30(3):109-20. (PMID: 19941415) Biotechniques. 2007 Sep;43(3):354-9. (PMID: 17907578) J Proteome Res. 2013 Jun 7;12(6):3010-8. (PMID: 23672200) J Neurosci. 2011 Aug 3;31(31):11231-43. (PMID: 21813684) Annu Rev Genet. 1999;33:89-131. (PMID: 10690405) Biophys J. 2007 May 1;92(9):3207-14. (PMID: 17218469) Proc Natl Acad Sci U S A. 2002 Jul 23;99(15):9755-60. (PMID: 12119397) J Neurosci. 2011 Oct 12;31(41):14660-8. (PMID: 21994382) Channels (Austin). 2014;8(6):528-35. (PMID: 25616687) Trends Cell Biol. 2020 Nov;30(11):904-915. (PMID: 32900570) Prog Retin Eye Res. 2016 Nov;55:52-81. (PMID: 27260426) Elife. 2015 Nov 21;4:. (PMID: 26590321) Methods Enzymol. 2000;316:50-64. (PMID: 10800668) Vision Res. 1998 May;38(10):1315-23. (PMID: 9666999) J Biol Chem. 2001 Dec 21;276(51):48009-16. (PMID: 11641407) J Neurosci. 1994 Oct;14(10):5818-33. (PMID: 7523628) Mol Biol Cell. 2014 Sep 1;25(17):2644-9. (PMID: 25009288) J Biol Chem. 1997 Apr 11;272(15):10303-10. (PMID: 9092582) Nature. 1989 Dec 14;342(6251):762-6. (PMID: 2481236) Proc Natl Acad Sci U S A. 2019 Dec 16;:. (PMID: 31843915) Sci Rep. 2017 Feb 15;7:42545. (PMID: 28198469) J Neurosci. 2014 Oct 15;34(42):13976-87. (PMID: 25319694) Methods Mol Biol. 1999;97:393-414. (PMID: 10443381) J Biol Chem. 1991 Nov 15;266(32):21917-22. (PMID: 1718987) J Neurosci. 2004 Mar 17;24(11):2623-32. (PMID: 15028754) J Neurosci. 2009 Aug 26;29(34):10541-51. (PMID: 19710307) Mol Cell Neurosci. 2003 Nov;24(3):687-95. (PMID: 14664818) J Biol Chem. 1996 Dec 20;271(51):32968-74. (PMID: 8955140) J Cell Biol. 2008 Nov 3;183(3):485-98. (PMID: 18981232) J Cell Biol. 2017 Sep 4;216(9):2927-2943. (PMID: 28743825) Neuron. 2002 Dec 5;36(5):891-6. (PMID: 12467592) Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3116-9. (PMID: 2014230) J Biol Chem. 2004 Jan 16;279(3):1581-4. (PMID: 14625292) Biochemistry. 1990 Feb 13;29(6):1601-7. (PMID: 2334719) Neuron. 2002 Dec 5;36(5):881-9. (PMID: 12467591) J Biol Chem. 1998 Apr 10;273(15):9148-57. (PMID: 9535905) Genomics. 1995 Jul 1;28(1):32-8. (PMID: 7590744) Prog Retin Eye Res. 2013 Sep;36:24-51. (PMID: 23562855) Neuron. 2002 Apr 11;34(2):197-207. (PMID: 11970862) EMBO J. 1998 Apr 15;17(8):2273-84. (PMID: 9545240) Proc Natl Acad Sci U S A. 2012 Jan 3;109(1):203-8. (PMID: 22184246) Proc Natl Acad Sci U S A. 2007 Jan 16;104(3):1027-32. (PMID: 17209010) J Cell Biol. 2017 May 1;216(5):1489-1499. (PMID: 28381413) Neuron. 2006 Aug 17;51(4):409-16. (PMID: 16908407) Biochemistry. 2016 Sep 13;55(36):5028-37. (PMID: 27509380) Biochemistry. 2011 Aug 16;50(32):6855-66. (PMID: 21721517) Science. 2009 Mar 20;323(5921):1614-7. (PMID: 19299621) J Biol Chem. 2006 Jan 20;281(3):1449-60. (PMID: 16280326) J Cell Biol. 1987 Dec;105(6 Pt 1):2589-601. (PMID: 2447095) |
معلومات مُعتمدة: | P30 EY005722 United States EY NEI NIH HHS; R01 EY030451 United States EY NEI NIH HHS; K99 EY025732 United States EY NEI NIH HHS; P30 EY007003 United States EY NEI NIH HHS; R01 EY012859 United States EY NEI NIH HHS; F31 EY007003 United States EY NEI NIH HHS; R00 EY025732 United States EY NEI NIH HHS |
فهرسة مساهمة: | Keywords: CNG channel; cilium; membrane trafficking; outer segment; photoreceptor |
المشرفين على المادة: | 0 (Cngb1 protein, mouse) 0 (Cyclic Nucleotide-Gated Cation Channels) 0 (Lrrc32 protein, mouse) 0 (Membrane Proteins) 0 (Nerve Tissue Proteins) |
تواريخ الأحداث: | Date Created: 20210227 Date Completed: 20210817 Latest Revision: 20211008 |
رمز التحديث: | 20221213 |
مُعرف محوري في PubMed: | PMC8026354 |
DOI: | 10.1523/JNEUROSCI.2609-20.2021 |
PMID: | 33637563 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1529-2401 |
---|---|
DOI: | 10.1523/JNEUROSCI.2609-20.2021 |