Deactivation Kinetics of the Transduction Cascade of Vision
The response of the retinal rod cell to a dim flash lasts less than a second. This phototransduction is mediated by a guanine nucleotide-binding (G) protein cascade in which rhodopsin is the receptor, transducin is the G-protein, and the cGMP-specific phosphodiesterase (PDE) is the effector. Photoex...
Gespeichert in:
Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 1991-11, Vol.88 (21), p.9813-9817 |
---|---|
Hauptverfasser: | , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 9817 |
---|---|
container_issue | 21 |
container_start_page | 9813 |
container_title | Proceedings of the National Academy of Sciences - PNAS |
container_volume | 88 |
creator | Vuong, T. Minh Chabre, Marc |
description | The response of the retinal rod cell to a dim flash lasts less than a second. This phototransduction is mediated by a guanine nucleotide-binding (G) protein cascade in which rhodopsin is the receptor, transducin is the G-protein, and the cGMP-specific phosphodiesterase (PDE) is the effector. Photoexcited rhodopsin activates transducin which in turn activates PDE. For this underlying biochemistry to be kinetically compatible with the photoresponse, both transducin and PDE must be deactivated in subsecond times. We report here direct measurements of their deactivation kinetics. The rate of heat release when transducin and PDE hydrolyze, respectively, GTP and cGMP was measured using time-resolved microcalorimetry. With only GTP present, the heat pulse comes from the activation of transducin and its subsequent deactivation by endogenous GTP hydrolysis. The nonhydrolyzable analog guanine 5'-[γ-thio]triphosphate was used to distinguish between these two processes: about 40% of the total heat is due to activation. From the time course of the deactivation heat, the active lifetime of transducin is |
doi_str_mv | 10.1073/pnas.88.21.9813 |
format | Article |
fullrecord | <record><control><sourceid>jstor_pnas_</sourceid><recordid>TN_cdi_pnas_primary_88_21_9813</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><jstor_id>2357896</jstor_id><sourcerecordid>2357896</sourcerecordid><originalsourceid>FETCH-LOGICAL-c522t-cc8e1eea104696d24b3547298e1d55f59e43f629e2044ac92faf2cebb72158213</originalsourceid><addsrcrecordid>eNqFkc1vEzEQxS0EKmngzAVQDhWcNrXHH2uLXqpAAVGJS-FqOd4xdbXZDWtvBf89XpIGegFfLM37zXj8HiHPGF0yWvPTbefSUuslsKXRjD8gM0YNq5Qw9CGZUQp1pQWIx-Q4pRtKqZGaHpEjpqSutZmRN2_R-RxvXY59t_gUO8zRp0UfFvkaF1eD61Iz-t_iyiXvGpy0rzGVyhPyKLg24dP9PSdfLt5drT5Ul5_ff1ydX1ZeAuTKe40M0TEqlFENiDWXogZTqo2UQRoUPCgwCFQI5w0EF8Djel0DkxoYn5Oz3dztuN5g47HLg2vtdogbN_y0vYv2vtLFa_utv7USNJvaX-3bh_77iCnbTUwe29Z12I_J1iAU1_X_Qaao0rycOTndgX7oUxowHHZh1E6x2CkWq7UFZqdYSseLv7_wh9_lUPSTvT6Z3Ibiu4_pgEmqRHGoYC_32DT_Tr33zut_AjaMbZvxRy7k8x15k3I_HFDgsuyj-C-WWLdc</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>16068333</pqid></control><display><type>article</type><title>Deactivation Kinetics of the Transduction Cascade of Vision</title><source>MEDLINE</source><source>JSTOR Archive Collection A-Z Listing</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><source>Free Full-Text Journals in Chemistry</source><creator>Vuong, T. Minh ; Chabre, Marc</creator><creatorcontrib>Vuong, T. Minh ; Chabre, Marc</creatorcontrib><description>The response of the retinal rod cell to a dim flash lasts less than a second. This phototransduction is mediated by a guanine nucleotide-binding (G) protein cascade in which rhodopsin is the receptor, transducin is the G-protein, and the cGMP-specific phosphodiesterase (PDE) is the effector. Photoexcited rhodopsin activates transducin which in turn activates PDE. For this underlying biochemistry to be kinetically compatible with the photoresponse, both transducin and PDE must be deactivated in subsecond times. We report here direct measurements of their deactivation kinetics. The rate of heat release when transducin and PDE hydrolyze, respectively, GTP and cGMP was measured using time-resolved microcalorimetry. With only GTP present, the heat pulse comes from the activation of transducin and its subsequent deactivation by endogenous GTP hydrolysis. The nonhydrolyzable analog guanine 5'-[γ-thio]triphosphate was used to distinguish between these two processes: about 40% of the total heat is due to activation. From the time course of the deactivation heat, the active lifetime of transducin is <1 s at 22⚬C. With both GTP and cGMP present, the highly amplified hydrolytic activity of the PDE is responsible for most of the heat produced; its rate of release is directly proportional to the amount of activated PDE. Measurements of this rate at low photoexcitation levels (e.g., 30 molecules of photoexcited rhodopsin per rod) provide much kinetic information about the cascade. Notably, deactivation of the PDE takes 0.6 s (at 23⚬C) and absolutely requires GTP hydrolysis. This concurs with the subsecond lifetime of active transducin and means that, once GTP hydrolysis has occurred, the hitherto active PDE is quickly inhibited.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.88.21.9813</identifier><identifier>PMID: 1658789</identifier><identifier>CODEN: PNASA6</identifier><language>eng</language><publisher>Washington, DC: National Academy of Sciences of the United States of America</publisher><subject>3',5'-Cyclic-GMP Phosphodiesterases - metabolism ; 3',5'-cyclic-nucleotide phosphodiesterase ; Animals ; Biochemistry ; Biological and medical sciences ; Biophysics ; Calorimetry ; Cattle ; Cell physiology ; Equilibrium flow ; Fundamental and applied biological sciences. Psychology ; Guanosine Triphosphate - metabolism ; Heat ; Hydrolysis ; In Vitro Techniques ; Kinetics ; Molecular and cellular biology ; Nucleotides ; Photochemistry ; Photoexcitation ; Receptors ; Rod Cell Outer Segment - metabolism ; Signal reflection ; Thermodynamics ; transducin ; Transducin - metabolism ; Vision, Ocular ; Vision, photoreception</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1991-11, Vol.88 (21), p.9813-9817</ispartof><rights>Copyright 1991 The National Academy of Sciences of the United States of America</rights><rights>1992 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c522t-cc8e1eea104696d24b3547298e1d55f59e43f629e2044ac92faf2cebb72158213</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/88/21.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/2357896$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/2357896$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,727,780,784,803,885,27923,27924,53790,53792,58016,58249</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=5064629$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1658789$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Vuong, T. Minh</creatorcontrib><creatorcontrib>Chabre, Marc</creatorcontrib><title>Deactivation Kinetics of the Transduction Cascade of Vision</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>The response of the retinal rod cell to a dim flash lasts less than a second. This phototransduction is mediated by a guanine nucleotide-binding (G) protein cascade in which rhodopsin is the receptor, transducin is the G-protein, and the cGMP-specific phosphodiesterase (PDE) is the effector. Photoexcited rhodopsin activates transducin which in turn activates PDE. For this underlying biochemistry to be kinetically compatible with the photoresponse, both transducin and PDE must be deactivated in subsecond times. We report here direct measurements of their deactivation kinetics. The rate of heat release when transducin and PDE hydrolyze, respectively, GTP and cGMP was measured using time-resolved microcalorimetry. With only GTP present, the heat pulse comes from the activation of transducin and its subsequent deactivation by endogenous GTP hydrolysis. The nonhydrolyzable analog guanine 5'-[γ-thio]triphosphate was used to distinguish between these two processes: about 40% of the total heat is due to activation. From the time course of the deactivation heat, the active lifetime of transducin is <1 s at 22⚬C. With both GTP and cGMP present, the highly amplified hydrolytic activity of the PDE is responsible for most of the heat produced; its rate of release is directly proportional to the amount of activated PDE. Measurements of this rate at low photoexcitation levels (e.g., 30 molecules of photoexcited rhodopsin per rod) provide much kinetic information about the cascade. Notably, deactivation of the PDE takes 0.6 s (at 23⚬C) and absolutely requires GTP hydrolysis. This concurs with the subsecond lifetime of active transducin and means that, once GTP hydrolysis has occurred, the hitherto active PDE is quickly inhibited.</description><subject>3',5'-Cyclic-GMP Phosphodiesterases - metabolism</subject><subject>3',5'-cyclic-nucleotide phosphodiesterase</subject><subject>Animals</subject><subject>Biochemistry</subject><subject>Biological and medical sciences</subject><subject>Biophysics</subject><subject>Calorimetry</subject><subject>Cattle</subject><subject>Cell physiology</subject><subject>Equilibrium flow</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Guanosine Triphosphate - metabolism</subject><subject>Heat</subject><subject>Hydrolysis</subject><subject>In Vitro Techniques</subject><subject>Kinetics</subject><subject>Molecular and cellular biology</subject><subject>Nucleotides</subject><subject>Photochemistry</subject><subject>Photoexcitation</subject><subject>Receptors</subject><subject>Rod Cell Outer Segment - metabolism</subject><subject>Signal reflection</subject><subject>Thermodynamics</subject><subject>transducin</subject><subject>Transducin - metabolism</subject><subject>Vision, Ocular</subject><subject>Vision, photoreception</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1991</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1vEzEQxS0EKmngzAVQDhWcNrXHH2uLXqpAAVGJS-FqOd4xdbXZDWtvBf89XpIGegFfLM37zXj8HiHPGF0yWvPTbefSUuslsKXRjD8gM0YNq5Qw9CGZUQp1pQWIx-Q4pRtKqZGaHpEjpqSutZmRN2_R-RxvXY59t_gUO8zRp0UfFvkaF1eD61Iz-t_iyiXvGpy0rzGVyhPyKLg24dP9PSdfLt5drT5Ul5_ff1ydX1ZeAuTKe40M0TEqlFENiDWXogZTqo2UQRoUPCgwCFQI5w0EF8Djel0DkxoYn5Oz3dztuN5g47HLg2vtdogbN_y0vYv2vtLFa_utv7USNJvaX-3bh_77iCnbTUwe29Z12I_J1iAU1_X_Qaao0rycOTndgX7oUxowHHZh1E6x2CkWq7UFZqdYSseLv7_wh9_lUPSTvT6Z3Ibiu4_pgEmqRHGoYC_32DT_Tr33zut_AjaMbZvxRy7k8x15k3I_HFDgsuyj-C-WWLdc</recordid><startdate>19911101</startdate><enddate>19911101</enddate><creator>Vuong, T. Minh</creator><creator>Chabre, Marc</creator><general>National Academy of Sciences of the United States of America</general><general>National Acad Sciences</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FD</scope><scope>FR3</scope><scope>M7Z</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19911101</creationdate><title>Deactivation Kinetics of the Transduction Cascade of Vision</title><author>Vuong, T. Minh ; Chabre, Marc</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c522t-cc8e1eea104696d24b3547298e1d55f59e43f629e2044ac92faf2cebb72158213</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1991</creationdate><topic>3',5'-Cyclic-GMP Phosphodiesterases - metabolism</topic><topic>3',5'-cyclic-nucleotide phosphodiesterase</topic><topic>Animals</topic><topic>Biochemistry</topic><topic>Biological and medical sciences</topic><topic>Biophysics</topic><topic>Calorimetry</topic><topic>Cattle</topic><topic>Cell physiology</topic><topic>Equilibrium flow</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Guanosine Triphosphate - metabolism</topic><topic>Heat</topic><topic>Hydrolysis</topic><topic>In Vitro Techniques</topic><topic>Kinetics</topic><topic>Molecular and cellular biology</topic><topic>Nucleotides</topic><topic>Photochemistry</topic><topic>Photoexcitation</topic><topic>Receptors</topic><topic>Rod Cell Outer Segment - metabolism</topic><topic>Signal reflection</topic><topic>Thermodynamics</topic><topic>transducin</topic><topic>Transducin - metabolism</topic><topic>Vision, Ocular</topic><topic>Vision, photoreception</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Vuong, T. Minh</creatorcontrib><creatorcontrib>Chabre, Marc</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biochemistry Abstracts 1</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vuong, T. Minh</au><au>Chabre, Marc</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Deactivation Kinetics of the Transduction Cascade of Vision</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>1991-11-01</date><risdate>1991</risdate><volume>88</volume><issue>21</issue><spage>9813</spage><epage>9817</epage><pages>9813-9817</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><coden>PNASA6</coden><abstract>The response of the retinal rod cell to a dim flash lasts less than a second. This phototransduction is mediated by a guanine nucleotide-binding (G) protein cascade in which rhodopsin is the receptor, transducin is the G-protein, and the cGMP-specific phosphodiesterase (PDE) is the effector. Photoexcited rhodopsin activates transducin which in turn activates PDE. For this underlying biochemistry to be kinetically compatible with the photoresponse, both transducin and PDE must be deactivated in subsecond times. We report here direct measurements of their deactivation kinetics. The rate of heat release when transducin and PDE hydrolyze, respectively, GTP and cGMP was measured using time-resolved microcalorimetry. With only GTP present, the heat pulse comes from the activation of transducin and its subsequent deactivation by endogenous GTP hydrolysis. The nonhydrolyzable analog guanine 5'-[γ-thio]triphosphate was used to distinguish between these two processes: about 40% of the total heat is due to activation. From the time course of the deactivation heat, the active lifetime of transducin is <1 s at 22⚬C. With both GTP and cGMP present, the highly amplified hydrolytic activity of the PDE is responsible for most of the heat produced; its rate of release is directly proportional to the amount of activated PDE. Measurements of this rate at low photoexcitation levels (e.g., 30 molecules of photoexcited rhodopsin per rod) provide much kinetic information about the cascade. Notably, deactivation of the PDE takes 0.6 s (at 23⚬C) and absolutely requires GTP hydrolysis. This concurs with the subsecond lifetime of active transducin and means that, once GTP hydrolysis has occurred, the hitherto active PDE is quickly inhibited.</abstract><cop>Washington, DC</cop><pub>National Academy of Sciences of the United States of America</pub><pmid>1658789</pmid><doi>10.1073/pnas.88.21.9813</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0027-8424 |
ispartof | Proceedings of the National Academy of Sciences - PNAS, 1991-11, Vol.88 (21), p.9813-9817 |
issn | 0027-8424 1091-6490 |
language | eng |
recordid | cdi_pnas_primary_88_21_9813 |
source | MEDLINE; JSTOR Archive Collection A-Z Listing; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
subjects | 3',5'-Cyclic-GMP Phosphodiesterases - metabolism 3',5'-cyclic-nucleotide phosphodiesterase Animals Biochemistry Biological and medical sciences Biophysics Calorimetry Cattle Cell physiology Equilibrium flow Fundamental and applied biological sciences. Psychology Guanosine Triphosphate - metabolism Heat Hydrolysis In Vitro Techniques Kinetics Molecular and cellular biology Nucleotides Photochemistry Photoexcitation Receptors Rod Cell Outer Segment - metabolism Signal reflection Thermodynamics transducin Transducin - metabolism Vision, Ocular Vision, photoreception |
title | Deactivation Kinetics of the Transduction Cascade of Vision |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-08T22%3A58%3A42IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-jstor_pnas_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Deactivation%20Kinetics%20of%20the%20Transduction%20Cascade%20of%20Vision&rft.jtitle=Proceedings%20of%20the%20National%20Academy%20of%20Sciences%20-%20PNAS&rft.au=Vuong,%20T.%20Minh&rft.date=1991-11-01&rft.volume=88&rft.issue=21&rft.spage=9813&rft.epage=9817&rft.pages=9813-9817&rft.issn=0027-8424&rft.eissn=1091-6490&rft.coden=PNASA6&rft_id=info:doi/10.1073/pnas.88.21.9813&rft_dat=%3Cjstor_pnas_%3E2357896%3C/jstor_pnas_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=16068333&rft_id=info:pmid/1658789&rft_jstor_id=2357896&rfr_iscdi=true |