Absolute proteomic quantification reveals design principles of sperm flagellar chemosensation
Cilia serve as cellular antennae that translate sensory information into physiological responses. In the sperm flagellum, a single chemoattractant molecule can trigger a Ca 2+ rise that controls motility. The mechanisms underlying such ultra‐sensitivity are ill‐defined. Here, we determine by mass sp...
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| creator | Trötschel, Christian Hamzeh, Hussein Alvarez, Luis Pascal, René Lavryk, Fedir Bönigk, Wolfgang Körschen, Heinz G Müller, Astrid Poetsch, Ansgar Rennhack, Andreas Gui, Long Nicastro, Daniela Strünker, Timo Seifert, Reinhard Kaupp, U Benjamin |
| description | Cilia serve as cellular antennae that translate sensory information into physiological responses. In the sperm flagellum, a single chemoattractant molecule can trigger a Ca
2+
rise that controls motility. The mechanisms underlying such ultra‐sensitivity are ill‐defined. Here, we determine by mass spectrometry the copy number of nineteen chemosensory signaling proteins in sperm flagella from the sea urchin
Arbacia punctulata
. Proteins are up to 1,000‐fold more abundant than the free cellular messengers cAMP, cGMP, H
+
, and Ca
2+
. Opto‐chemical techniques show that high protein concentrations kinetically compartmentalize the flagellum: Within milliseconds, cGMP is relayed from the receptor guanylate cyclase to a cGMP‐gated channel that serves as a perfect chemo‐electrical transducer. cGMP is rapidly hydrolyzed, possibly via “substrate channeling” from the channel to the phosphodiesterase PDE5. The channel/PDE5 tandem encodes cGMP turnover rates rather than concentrations. The rate‐detection mechanism allows continuous stimulus sampling over a wide dynamic range. The textbook notion of signal amplification—few enzyme molecules process many messenger molecules—does not hold for sperm flagella. Instead, high protein concentrations ascertain messenger detection. Similar mechanisms may occur in other small compartments like primary cilia or dendritic spines.
Synopsis
Cellular sensory compartments serve highly specialised functions by means of a unique repertoire of signalling proteins. Here, quantitative protein profiling combined with structural analyses in sea urchin sperm flagella reveal reversed enzyme‐messenger ratios in chemosensory signalling, which ensure high‐sensitivity, low‐noise messenger detection.
Absolute quantification of 11 chemosensory signaling proteins is applied to purified flagella of
Arbacia punctulata
.
Determination of flagellar volume by cryo‐electron tomography allows for calculation of protein concentrations.
Signaling proteins are orders of magnitude more abundant than free messengers.
Opto‐chemical techniques show kinetic compartmentalisation of the flagellum at the cGMP‐gated channel/PDE5 tandem.
Graphical Abstract
Reversed enzyme‐messenger ratios in sperm cilia ensure high‐sensitivity, low noise messenger detection. |
| doi_str_mv | 10.15252/embj.2019102723 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7024835</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2331249498</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5193-f042f3aad3a70ae8237f5d707486c170438f4714fc177942b7ee833358253ba23</originalsourceid><addsrcrecordid>eNqFkc9LHDEcxUOx1K1676kMeOllND83GSiCFdtaFC96lJDJfrNmmUnWZEbxvzfr-qMWiqfwJZ_3eI-H0BeC94iggu5D3y72KCYNwVRS9gFNCJ_immIpNtAE0ympOVHNJvqc8wJjLJQkn9AmI0qVi0_Q1WGbYzcOUC1THCD23lY3owmDd96awcdQJbgF0-VqBtnPQ-F8sH7ZQa6iq_ISUl-5zsyh60yq7DX0MUPIj9pt9NEVKew8vVvo8ufxxdHv-vT818nR4WltBWlY7TCnjhkzY0ZiA4oy6cRMYsnV1BKJOVOOS8JdOWTDaSsBFGNMKCpYayjbQgdr3-XY9jCzEIZkOl2i9ibd62i8fvsT_LWex1stMeWKiWLw7ckgxZsR8qB7n-2qUoA4Zk0ZI5Q3vFEF3f0HXcQxhVKvUEJIxajghcJryqaYcwL3EoZg_bidXm2nX7crkq9_l3gRPI9VgO9r4M53cP-uoT4--_HnjT9Zy_Nqwjmk1-D_zfQA90S35A</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2355783254</pqid></control><display><type>article</type><title>Absolute proteomic quantification reveals design principles of sperm flagellar chemosensation</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Springer Nature OA Free Journals</source><source>Wiley Free Content</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Trötschel, Christian ; Hamzeh, Hussein ; Alvarez, Luis ; Pascal, René ; Lavryk, Fedir ; Bönigk, Wolfgang ; Körschen, Heinz G ; Müller, Astrid ; Poetsch, Ansgar ; Rennhack, Andreas ; Gui, Long ; Nicastro, Daniela ; Strünker, Timo ; Seifert, Reinhard ; Kaupp, U Benjamin</creator><creatorcontrib>Trötschel, Christian ; Hamzeh, Hussein ; Alvarez, Luis ; Pascal, René ; Lavryk, Fedir ; Bönigk, Wolfgang ; Körschen, Heinz G ; Müller, Astrid ; Poetsch, Ansgar ; Rennhack, Andreas ; Gui, Long ; Nicastro, Daniela ; Strünker, Timo ; Seifert, Reinhard ; Kaupp, U Benjamin</creatorcontrib><description>Cilia serve as cellular antennae that translate sensory information into physiological responses. In the sperm flagellum, a single chemoattractant molecule can trigger a Ca
2+
rise that controls motility. The mechanisms underlying such ultra‐sensitivity are ill‐defined. Here, we determine by mass spectrometry the copy number of nineteen chemosensory signaling proteins in sperm flagella from the sea urchin
Arbacia punctulata
. Proteins are up to 1,000‐fold more abundant than the free cellular messengers cAMP, cGMP, H
+
, and Ca
2+
. Opto‐chemical techniques show that high protein concentrations kinetically compartmentalize the flagellum: Within milliseconds, cGMP is relayed from the receptor guanylate cyclase to a cGMP‐gated channel that serves as a perfect chemo‐electrical transducer. cGMP is rapidly hydrolyzed, possibly via “substrate channeling” from the channel to the phosphodiesterase PDE5. The channel/PDE5 tandem encodes cGMP turnover rates rather than concentrations. The rate‐detection mechanism allows continuous stimulus sampling over a wide dynamic range. The textbook notion of signal amplification—few enzyme molecules process many messenger molecules—does not hold for sperm flagella. Instead, high protein concentrations ascertain messenger detection. Similar mechanisms may occur in other small compartments like primary cilia or dendritic spines.
Synopsis
Cellular sensory compartments serve highly specialised functions by means of a unique repertoire of signalling proteins. Here, quantitative protein profiling combined with structural analyses in sea urchin sperm flagella reveal reversed enzyme‐messenger ratios in chemosensory signalling, which ensure high‐sensitivity, low‐noise messenger detection.
Absolute quantification of 11 chemosensory signaling proteins is applied to purified flagella of
Arbacia punctulata
.
Determination of flagellar volume by cryo‐electron tomography allows for calculation of protein concentrations.
Signaling proteins are orders of magnitude more abundant than free messengers.
Opto‐chemical techniques show kinetic compartmentalisation of the flagellum at the cGMP‐gated channel/PDE5 tandem.
Graphical Abstract
Reversed enzyme‐messenger ratios in sperm cilia ensure high‐sensitivity, low noise messenger detection.</description><identifier>ISSN: 0261-4189</identifier><identifier>ISSN: 1460-2075</identifier><identifier>EISSN: 1460-2075</identifier><identifier>DOI: 10.15252/embj.2019102723</identifier><identifier>PMID: 31880004</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Animals ; Antennae ; Arbacia - physiology ; Arbacia - ultrastructure ; Arbacia punctulata ; Calcium ; Calcium - metabolism ; Calcium ions ; Channeling ; Chemoreception ; Chemotaxis ; Cilia ; Cilia - physiology ; Cilia - ultrastructure ; cilium ; Compartments ; Copy number ; Cyclic GMP ; Cyclic GMP - metabolism ; Dendritic spines ; Electron Microscope Tomography ; electron tomography ; EMBO27 ; EMBO37 ; Enzymes ; fertilization ; Flagella ; Flagella - physiology ; Flagella - ultrastructure ; Guanylate cyclase ; Guanylate Cyclase - metabolism ; Male ; Mass Spectrometry ; Mass spectroscopy ; Noise sensitivity ; Organic chemistry ; Phosphodiesterase ; Physiological responses ; Proteins ; Proteomics ; quantitative mass spectrometry ; Signal processing ; Signal Transduction ; Signaling ; Sperm ; Spermatozoa - physiology ; Spermatozoa - ultrastructure ; Substrates</subject><ispartof>The EMBO journal, 2020-02, Vol.39 (4), p.e102723-n/a</ispartof><rights>The Author(s) 2019</rights><rights>2019 The Authors. Published under the terms of the CC BY NC ND 4.0 license</rights><rights>2019 The Authors. Published under the terms of the CC BY NC ND 4.0 license.</rights><rights>2020 EMBO</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5193-f042f3aad3a70ae8237f5d707486c170438f4714fc177942b7ee833358253ba23</citedby><cites>FETCH-LOGICAL-c5193-f042f3aad3a70ae8237f5d707486c170438f4714fc177942b7ee833358253ba23</cites><orcidid>0000-0002-3056-788X ; 0000-0002-9607-1123 ; 0000-0003-0812-1547 ; 0000-0002-7540-3475 ; 0000-0002-0696-6397</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7024835/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7024835/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,1416,1432,27915,27916,41111,42180,45565,45566,46400,46824,51567,53782,53784</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31880004$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Trötschel, Christian</creatorcontrib><creatorcontrib>Hamzeh, Hussein</creatorcontrib><creatorcontrib>Alvarez, Luis</creatorcontrib><creatorcontrib>Pascal, René</creatorcontrib><creatorcontrib>Lavryk, Fedir</creatorcontrib><creatorcontrib>Bönigk, Wolfgang</creatorcontrib><creatorcontrib>Körschen, Heinz G</creatorcontrib><creatorcontrib>Müller, Astrid</creatorcontrib><creatorcontrib>Poetsch, Ansgar</creatorcontrib><creatorcontrib>Rennhack, Andreas</creatorcontrib><creatorcontrib>Gui, Long</creatorcontrib><creatorcontrib>Nicastro, Daniela</creatorcontrib><creatorcontrib>Strünker, Timo</creatorcontrib><creatorcontrib>Seifert, Reinhard</creatorcontrib><creatorcontrib>Kaupp, U Benjamin</creatorcontrib><title>Absolute proteomic quantification reveals design principles of sperm flagellar chemosensation</title><title>The EMBO journal</title><addtitle>EMBO J</addtitle><addtitle>EMBO J</addtitle><description>Cilia serve as cellular antennae that translate sensory information into physiological responses. In the sperm flagellum, a single chemoattractant molecule can trigger a Ca
2+
rise that controls motility. The mechanisms underlying such ultra‐sensitivity are ill‐defined. Here, we determine by mass spectrometry the copy number of nineteen chemosensory signaling proteins in sperm flagella from the sea urchin
Arbacia punctulata
. Proteins are up to 1,000‐fold more abundant than the free cellular messengers cAMP, cGMP, H
+
, and Ca
2+
. Opto‐chemical techniques show that high protein concentrations kinetically compartmentalize the flagellum: Within milliseconds, cGMP is relayed from the receptor guanylate cyclase to a cGMP‐gated channel that serves as a perfect chemo‐electrical transducer. cGMP is rapidly hydrolyzed, possibly via “substrate channeling” from the channel to the phosphodiesterase PDE5. The channel/PDE5 tandem encodes cGMP turnover rates rather than concentrations. The rate‐detection mechanism allows continuous stimulus sampling over a wide dynamic range. The textbook notion of signal amplification—few enzyme molecules process many messenger molecules—does not hold for sperm flagella. Instead, high protein concentrations ascertain messenger detection. Similar mechanisms may occur in other small compartments like primary cilia or dendritic spines.
Synopsis
Cellular sensory compartments serve highly specialised functions by means of a unique repertoire of signalling proteins. Here, quantitative protein profiling combined with structural analyses in sea urchin sperm flagella reveal reversed enzyme‐messenger ratios in chemosensory signalling, which ensure high‐sensitivity, low‐noise messenger detection.
Absolute quantification of 11 chemosensory signaling proteins is applied to purified flagella of
Arbacia punctulata
.
Determination of flagellar volume by cryo‐electron tomography allows for calculation of protein concentrations.
Signaling proteins are orders of magnitude more abundant than free messengers.
Opto‐chemical techniques show kinetic compartmentalisation of the flagellum at the cGMP‐gated channel/PDE5 tandem.
Graphical Abstract
Reversed enzyme‐messenger ratios in sperm cilia ensure high‐sensitivity, low noise messenger detection.</description><subject>Animals</subject><subject>Antennae</subject><subject>Arbacia - physiology</subject><subject>Arbacia - ultrastructure</subject><subject>Arbacia punctulata</subject><subject>Calcium</subject><subject>Calcium - metabolism</subject><subject>Calcium ions</subject><subject>Channeling</subject><subject>Chemoreception</subject><subject>Chemotaxis</subject><subject>Cilia</subject><subject>Cilia - physiology</subject><subject>Cilia - ultrastructure</subject><subject>cilium</subject><subject>Compartments</subject><subject>Copy number</subject><subject>Cyclic GMP</subject><subject>Cyclic GMP - metabolism</subject><subject>Dendritic spines</subject><subject>Electron Microscope Tomography</subject><subject>electron tomography</subject><subject>EMBO27</subject><subject>EMBO37</subject><subject>Enzymes</subject><subject>fertilization</subject><subject>Flagella</subject><subject>Flagella - physiology</subject><subject>Flagella - ultrastructure</subject><subject>Guanylate cyclase</subject><subject>Guanylate Cyclase - metabolism</subject><subject>Male</subject><subject>Mass Spectrometry</subject><subject>Mass spectroscopy</subject><subject>Noise sensitivity</subject><subject>Organic chemistry</subject><subject>Phosphodiesterase</subject><subject>Physiological responses</subject><subject>Proteins</subject><subject>Proteomics</subject><subject>quantitative mass spectrometry</subject><subject>Signal processing</subject><subject>Signal Transduction</subject><subject>Signaling</subject><subject>Sperm</subject><subject>Spermatozoa - physiology</subject><subject>Spermatozoa - ultrastructure</subject><subject>Substrates</subject><issn>0261-4189</issn><issn>1460-2075</issn><issn>1460-2075</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><recordid>eNqFkc9LHDEcxUOx1K1676kMeOllND83GSiCFdtaFC96lJDJfrNmmUnWZEbxvzfr-qMWiqfwJZ_3eI-H0BeC94iggu5D3y72KCYNwVRS9gFNCJ_immIpNtAE0ympOVHNJvqc8wJjLJQkn9AmI0qVi0_Q1WGbYzcOUC1THCD23lY3owmDd96awcdQJbgF0-VqBtnPQ-F8sH7ZQa6iq_ISUl-5zsyh60yq7DX0MUPIj9pt9NEVKew8vVvo8ufxxdHv-vT818nR4WltBWlY7TCnjhkzY0ZiA4oy6cRMYsnV1BKJOVOOS8JdOWTDaSsBFGNMKCpYayjbQgdr3-XY9jCzEIZkOl2i9ibd62i8fvsT_LWex1stMeWKiWLw7ckgxZsR8qB7n-2qUoA4Zk0ZI5Q3vFEF3f0HXcQxhVKvUEJIxajghcJryqaYcwL3EoZg_bidXm2nX7crkq9_l3gRPI9VgO9r4M53cP-uoT4--_HnjT9Zy_Nqwjmk1-D_zfQA90S35A</recordid><startdate>20200217</startdate><enddate>20200217</enddate><creator>Trötschel, Christian</creator><creator>Hamzeh, Hussein</creator><creator>Alvarez, Luis</creator><creator>Pascal, René</creator><creator>Lavryk, Fedir</creator><creator>Bönigk, Wolfgang</creator><creator>Körschen, Heinz G</creator><creator>Müller, Astrid</creator><creator>Poetsch, Ansgar</creator><creator>Rennhack, Andreas</creator><creator>Gui, Long</creator><creator>Nicastro, Daniela</creator><creator>Strünker, Timo</creator><creator>Seifert, Reinhard</creator><creator>Kaupp, U Benjamin</creator><general>Nature Publishing Group UK</general><general>Blackwell Publishing Ltd</general><general>John Wiley and Sons Inc</general><scope>C6C</scope><scope>24P</scope><scope>WIN</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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-3056-788X</orcidid><orcidid>https://orcid.org/0000-0002-9607-1123</orcidid><orcidid>https://orcid.org/0000-0003-0812-1547</orcidid><orcidid>https://orcid.org/0000-0002-7540-3475</orcidid><orcidid>https://orcid.org/0000-0002-0696-6397</orcidid></search><sort><creationdate>20200217</creationdate><title>Absolute proteomic quantification reveals design principles of sperm flagellar chemosensation</title><author>Trötschel, Christian ; Hamzeh, Hussein ; Alvarez, Luis ; Pascal, René ; Lavryk, Fedir ; Bönigk, Wolfgang ; Körschen, Heinz G ; Müller, Astrid ; Poetsch, Ansgar ; Rennhack, Andreas ; Gui, Long ; Nicastro, Daniela ; Strünker, Timo ; Seifert, Reinhard ; Kaupp, U Benjamin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5193-f042f3aad3a70ae8237f5d707486c170438f4714fc177942b7ee833358253ba23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>Antennae</topic><topic>Arbacia - physiology</topic><topic>Arbacia - ultrastructure</topic><topic>Arbacia punctulata</topic><topic>Calcium</topic><topic>Calcium - metabolism</topic><topic>Calcium ions</topic><topic>Channeling</topic><topic>Chemoreception</topic><topic>Chemotaxis</topic><topic>Cilia</topic><topic>Cilia - physiology</topic><topic>Cilia - ultrastructure</topic><topic>cilium</topic><topic>Compartments</topic><topic>Copy number</topic><topic>Cyclic GMP</topic><topic>Cyclic GMP - metabolism</topic><topic>Dendritic spines</topic><topic>Electron Microscope Tomography</topic><topic>electron tomography</topic><topic>EMBO27</topic><topic>EMBO37</topic><topic>Enzymes</topic><topic>fertilization</topic><topic>Flagella</topic><topic>Flagella - physiology</topic><topic>Flagella - ultrastructure</topic><topic>Guanylate cyclase</topic><topic>Guanylate Cyclase - metabolism</topic><topic>Male</topic><topic>Mass Spectrometry</topic><topic>Mass spectroscopy</topic><topic>Noise sensitivity</topic><topic>Organic chemistry</topic><topic>Phosphodiesterase</topic><topic>Physiological responses</topic><topic>Proteins</topic><topic>Proteomics</topic><topic>quantitative mass spectrometry</topic><topic>Signal processing</topic><topic>Signal Transduction</topic><topic>Signaling</topic><topic>Sperm</topic><topic>Spermatozoa - physiology</topic><topic>Spermatozoa - ultrastructure</topic><topic>Substrates</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Trötschel, Christian</creatorcontrib><creatorcontrib>Hamzeh, Hussein</creatorcontrib><creatorcontrib>Alvarez, Luis</creatorcontrib><creatorcontrib>Pascal, René</creatorcontrib><creatorcontrib>Lavryk, Fedir</creatorcontrib><creatorcontrib>Bönigk, Wolfgang</creatorcontrib><creatorcontrib>Körschen, Heinz G</creatorcontrib><creatorcontrib>Müller, Astrid</creatorcontrib><creatorcontrib>Poetsch, Ansgar</creatorcontrib><creatorcontrib>Rennhack, Andreas</creatorcontrib><creatorcontrib>Gui, Long</creatorcontrib><creatorcontrib>Nicastro, Daniela</creatorcontrib><creatorcontrib>Strünker, Timo</creatorcontrib><creatorcontrib>Seifert, Reinhard</creatorcontrib><creatorcontrib>Kaupp, U Benjamin</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Wiley-Blackwell Open Access Titles</collection><collection>Wiley Free Content</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The EMBO journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Trötschel, Christian</au><au>Hamzeh, Hussein</au><au>Alvarez, Luis</au><au>Pascal, René</au><au>Lavryk, Fedir</au><au>Bönigk, Wolfgang</au><au>Körschen, Heinz G</au><au>Müller, Astrid</au><au>Poetsch, Ansgar</au><au>Rennhack, Andreas</au><au>Gui, Long</au><au>Nicastro, Daniela</au><au>Strünker, Timo</au><au>Seifert, Reinhard</au><au>Kaupp, U Benjamin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Absolute proteomic quantification reveals design principles of sperm flagellar chemosensation</atitle><jtitle>The EMBO journal</jtitle><stitle>EMBO J</stitle><addtitle>EMBO J</addtitle><date>2020-02-17</date><risdate>2020</risdate><volume>39</volume><issue>4</issue><spage>e102723</spage><epage>n/a</epage><pages>e102723-n/a</pages><issn>0261-4189</issn><issn>1460-2075</issn><eissn>1460-2075</eissn><abstract>Cilia serve as cellular antennae that translate sensory information into physiological responses. In the sperm flagellum, a single chemoattractant molecule can trigger a Ca
2+
rise that controls motility. The mechanisms underlying such ultra‐sensitivity are ill‐defined. Here, we determine by mass spectrometry the copy number of nineteen chemosensory signaling proteins in sperm flagella from the sea urchin
Arbacia punctulata
. Proteins are up to 1,000‐fold more abundant than the free cellular messengers cAMP, cGMP, H
+
, and Ca
2+
. Opto‐chemical techniques show that high protein concentrations kinetically compartmentalize the flagellum: Within milliseconds, cGMP is relayed from the receptor guanylate cyclase to a cGMP‐gated channel that serves as a perfect chemo‐electrical transducer. cGMP is rapidly hydrolyzed, possibly via “substrate channeling” from the channel to the phosphodiesterase PDE5. The channel/PDE5 tandem encodes cGMP turnover rates rather than concentrations. The rate‐detection mechanism allows continuous stimulus sampling over a wide dynamic range. The textbook notion of signal amplification—few enzyme molecules process many messenger molecules—does not hold for sperm flagella. Instead, high protein concentrations ascertain messenger detection. Similar mechanisms may occur in other small compartments like primary cilia or dendritic spines.
Synopsis
Cellular sensory compartments serve highly specialised functions by means of a unique repertoire of signalling proteins. Here, quantitative protein profiling combined with structural analyses in sea urchin sperm flagella reveal reversed enzyme‐messenger ratios in chemosensory signalling, which ensure high‐sensitivity, low‐noise messenger detection.
Absolute quantification of 11 chemosensory signaling proteins is applied to purified flagella of
Arbacia punctulata
.
Determination of flagellar volume by cryo‐electron tomography allows for calculation of protein concentrations.
Signaling proteins are orders of magnitude more abundant than free messengers.
Opto‐chemical techniques show kinetic compartmentalisation of the flagellum at the cGMP‐gated channel/PDE5 tandem.
Graphical Abstract
Reversed enzyme‐messenger ratios in sperm cilia ensure high‐sensitivity, low noise messenger detection.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>31880004</pmid><doi>10.15252/embj.2019102723</doi><tpages>18</tpages><orcidid>https://orcid.org/0000-0002-3056-788X</orcidid><orcidid>https://orcid.org/0000-0002-9607-1123</orcidid><orcidid>https://orcid.org/0000-0003-0812-1547</orcidid><orcidid>https://orcid.org/0000-0002-7540-3475</orcidid><orcidid>https://orcid.org/0000-0002-0696-6397</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0261-4189 |
| ispartof | The EMBO journal, 2020-02, Vol.39 (4), p.e102723-n/a |
| issn | 0261-4189 1460-2075 1460-2075 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7024835 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Springer Nature OA Free Journals; Wiley Free Content; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Animals Antennae Arbacia - physiology Arbacia - ultrastructure Arbacia punctulata Calcium Calcium - metabolism Calcium ions Channeling Chemoreception Chemotaxis Cilia Cilia - physiology Cilia - ultrastructure cilium Compartments Copy number Cyclic GMP Cyclic GMP - metabolism Dendritic spines Electron Microscope Tomography electron tomography EMBO27 EMBO37 Enzymes fertilization Flagella Flagella - physiology Flagella - ultrastructure Guanylate cyclase Guanylate Cyclase - metabolism Male Mass Spectrometry Mass spectroscopy Noise sensitivity Organic chemistry Phosphodiesterase Physiological responses Proteins Proteomics quantitative mass spectrometry Signal processing Signal Transduction Signaling Sperm Spermatozoa - physiology Spermatozoa - ultrastructure Substrates |
| title | Absolute proteomic quantification reveals design principles of sperm flagellar chemosensation |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-15T04%3A54%3A18IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Absolute%20proteomic%20quantification%20reveals%20design%20principles%20of%20sperm%20flagellar%20chemosensation&rft.jtitle=The%20EMBO%20journal&rft.au=Tr%C3%B6tschel,%20Christian&rft.date=2020-02-17&rft.volume=39&rft.issue=4&rft.spage=e102723&rft.epage=n/a&rft.pages=e102723-n/a&rft.issn=0261-4189&rft.eissn=1460-2075&rft_id=info:doi/10.15252/embj.2019102723&rft_dat=%3Cproquest_pubme%3E2331249498%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2355783254&rft_id=info:pmid/31880004&rfr_iscdi=true |