MARK2 phosphorylates KIF13A at a 14-3-3 binding site to polarize vesicular transport of transferrin receptor within dendrites
Neurons regulate the microtubule-based transport of certain vesicles selectively into axons or dendrites to ensure proper polarization of function. The mechanism of this polarized vesicle transport is still not fully elucidated, though it is known to involve kinesins, which drive anterograde transpo...
Gespeichert in:
| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2024-05, Vol.121 (20), p.e2316266121 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 20 |
| container_start_page | e2316266121 |
| container_title | Proceedings of the National Academy of Sciences - PNAS |
| container_volume | 121 |
| creator | Han, Yue Li, Min Zhao, Bingqing Wang, Huichao Liu, Yan Liu, Zhijun Xu, Jiaxi Yang, Rui |
| description | Neurons regulate the microtubule-based transport of certain vesicles selectively into axons or dendrites to ensure proper polarization of function. The mechanism of this polarized vesicle transport is still not fully elucidated, though it is known to involve kinesins, which drive anterograde transport on microtubules. Here, we explore how the kinesin-3 family member KIF13A is regulated such that vesicles containing transferrin receptor (TfR) travel only to dendrites. In experiments involving live-cell imaging, knockout of KIF13A, BioID assay, we found that the kinase MARK2 phosphorylates KIF13A at a 14-3-3 binding motif, strengthening interaction of KIF13A with 14-3-3 such that it dissociates from TfR-containing vesicles, which therefore cannot enter axons. Overexpression of KIF13A or knockout of MARK2 leads to axonal transport of TfR-containing vesicles. These results suggest a unique kinesin-based mechanism for polarized transport of vesicles to dendrites. |
| doi_str_mv | 10.1073/pnas.2316266121 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11098127</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3051939726</sourcerecordid><originalsourceid>FETCH-LOGICAL-c335t-1e7b9f2cbca1a559fc3c42e2158351e9fa0e202b0ee9afacb725f2d4cb461d2b3</originalsourceid><addsrcrecordid>eNpdkc1rVTEQxYMo9lm7dicBN25um0nuV1byKFZLK4Vi1yE3d9KXcl9yTXIrFfzfzePV-rEIw2F-OczMIeQNsGNgnTiZvU7HXEDL2xY4PCMrYBKqtpbsOVkxxruqr3l9QF6ldMcYk03PXpID0XdMSi5W5OeX9fUFp_MmpPLiw6QzJnpxfgZiTXWmmkJdiUrQwfnR-VuaXEaaA53DpKP7gfQekzNLETRH7dMcYqbB7oXFGJ2nEQ3OOUT63eVN0SP6MRaf9Jq8sHpKePRYD8nN2cevp5-ry6tP56fry8oI0eQKsBuk5WYwGnTTSGuEqTlyaHrRAEqrGXLGB4YotdVm6Hhj-ViboW5h5IM4JB_2vvMybHE06Mt4k5qj2-r4oIJ26t-Odxt1G-4VlHP2wLvi8P7RIYZvC6asti4ZnCbtMSxJCdaAFLLjbUHf_YfehSX6st-O6vu2BiELdbKnTAwpRbRP0wBTu2zVLlv1J9vy4-3fSzzxv8MUvwAjSqHi</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3058864139</pqid></control><display><type>article</type><title>MARK2 phosphorylates KIF13A at a 14-3-3 binding site to polarize vesicular transport of transferrin receptor within dendrites</title><source>MEDLINE</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><source>Free Full-Text Journals in Chemistry</source><creator>Han, Yue ; Li, Min ; Zhao, Bingqing ; Wang, Huichao ; Liu, Yan ; Liu, Zhijun ; Xu, Jiaxi ; Yang, Rui</creator><creatorcontrib>Han, Yue ; Li, Min ; Zhao, Bingqing ; Wang, Huichao ; Liu, Yan ; Liu, Zhijun ; Xu, Jiaxi ; Yang, Rui</creatorcontrib><description>Neurons regulate the microtubule-based transport of certain vesicles selectively into axons or dendrites to ensure proper polarization of function. The mechanism of this polarized vesicle transport is still not fully elucidated, though it is known to involve kinesins, which drive anterograde transport on microtubules. Here, we explore how the kinesin-3 family member KIF13A is regulated such that vesicles containing transferrin receptor (TfR) travel only to dendrites. In experiments involving live-cell imaging, knockout of KIF13A, BioID assay, we found that the kinase MARK2 phosphorylates KIF13A at a 14-3-3 binding motif, strengthening interaction of KIF13A with 14-3-3 such that it dissociates from TfR-containing vesicles, which therefore cannot enter axons. Overexpression of KIF13A or knockout of MARK2 leads to axonal transport of TfR-containing vesicles. These results suggest a unique kinesin-based mechanism for polarized transport of vesicles to dendrites.</description><identifier>ISSN: 0027-8424</identifier><identifier>ISSN: 1091-6490</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.2316266121</identifier><identifier>PMID: 38709923</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>14-3-3 protein ; 14-3-3 Proteins - metabolism ; Animals ; Anterograde transport ; Axonal transport ; Axons ; Binding Sites ; Biological Sciences ; Dendrites ; Dendrites - metabolism ; Humans ; Kinases ; Kinesin ; Kinesins - genetics ; Kinesins - metabolism ; Mice ; Microtubules ; Microtubules - metabolism ; Phosphorylation ; Protein Binding ; Protein Serine-Threonine Kinases - genetics ; Protein Serine-Threonine Kinases - metabolism ; Protein-serine/threonine kinase ; Rats ; Receptors ; Receptors, Transferrin - metabolism ; Transferrin ; Transferrins ; Vesicles</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2024-05, Vol.121 (20), p.e2316266121</ispartof><rights>Copyright National Academy of Sciences May 14, 2024</rights><rights>Copyright © 2024 the Author(s). Published by PNAS. 2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c335t-1e7b9f2cbca1a559fc3c42e2158351e9fa0e202b0ee9afacb725f2d4cb461d2b3</cites><orcidid>0009-0006-4661-0682 ; 0009-0002-9481-4322 ; 0009-0003-3731-840X ; 0009-0003-5170-6476 ; 0000-0003-1006-7893</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/PMC11098127/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11098127/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38709923$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Han, Yue</creatorcontrib><creatorcontrib>Li, Min</creatorcontrib><creatorcontrib>Zhao, Bingqing</creatorcontrib><creatorcontrib>Wang, Huichao</creatorcontrib><creatorcontrib>Liu, Yan</creatorcontrib><creatorcontrib>Liu, Zhijun</creatorcontrib><creatorcontrib>Xu, Jiaxi</creatorcontrib><creatorcontrib>Yang, Rui</creatorcontrib><title>MARK2 phosphorylates KIF13A at a 14-3-3 binding site to polarize vesicular transport of transferrin receptor within dendrites</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Neurons regulate the microtubule-based transport of certain vesicles selectively into axons or dendrites to ensure proper polarization of function. The mechanism of this polarized vesicle transport is still not fully elucidated, though it is known to involve kinesins, which drive anterograde transport on microtubules. Here, we explore how the kinesin-3 family member KIF13A is regulated such that vesicles containing transferrin receptor (TfR) travel only to dendrites. In experiments involving live-cell imaging, knockout of KIF13A, BioID assay, we found that the kinase MARK2 phosphorylates KIF13A at a 14-3-3 binding motif, strengthening interaction of KIF13A with 14-3-3 such that it dissociates from TfR-containing vesicles, which therefore cannot enter axons. Overexpression of KIF13A or knockout of MARK2 leads to axonal transport of TfR-containing vesicles. These results suggest a unique kinesin-based mechanism for polarized transport of vesicles to dendrites.</description><subject>14-3-3 protein</subject><subject>14-3-3 Proteins - metabolism</subject><subject>Animals</subject><subject>Anterograde transport</subject><subject>Axonal transport</subject><subject>Axons</subject><subject>Binding Sites</subject><subject>Biological Sciences</subject><subject>Dendrites</subject><subject>Dendrites - metabolism</subject><subject>Humans</subject><subject>Kinases</subject><subject>Kinesin</subject><subject>Kinesins - genetics</subject><subject>Kinesins - metabolism</subject><subject>Mice</subject><subject>Microtubules</subject><subject>Microtubules - metabolism</subject><subject>Phosphorylation</subject><subject>Protein Binding</subject><subject>Protein Serine-Threonine Kinases - genetics</subject><subject>Protein Serine-Threonine Kinases - metabolism</subject><subject>Protein-serine/threonine kinase</subject><subject>Rats</subject><subject>Receptors</subject><subject>Receptors, Transferrin - metabolism</subject><subject>Transferrin</subject><subject>Transferrins</subject><subject>Vesicles</subject><issn>0027-8424</issn><issn>1091-6490</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkc1rVTEQxYMo9lm7dicBN25um0nuV1byKFZLK4Vi1yE3d9KXcl9yTXIrFfzfzePV-rEIw2F-OczMIeQNsGNgnTiZvU7HXEDL2xY4PCMrYBKqtpbsOVkxxruqr3l9QF6ldMcYk03PXpID0XdMSi5W5OeX9fUFp_MmpPLiw6QzJnpxfgZiTXWmmkJdiUrQwfnR-VuaXEaaA53DpKP7gfQekzNLETRH7dMcYqbB7oXFGJ2nEQ3OOUT63eVN0SP6MRaf9Jq8sHpKePRYD8nN2cevp5-ry6tP56fry8oI0eQKsBuk5WYwGnTTSGuEqTlyaHrRAEqrGXLGB4YotdVm6Hhj-ViboW5h5IM4JB_2vvMybHE06Mt4k5qj2-r4oIJ26t-Odxt1G-4VlHP2wLvi8P7RIYZvC6asti4ZnCbtMSxJCdaAFLLjbUHf_YfehSX6st-O6vu2BiELdbKnTAwpRbRP0wBTu2zVLlv1J9vy4-3fSzzxv8MUvwAjSqHi</recordid><startdate>20240514</startdate><enddate>20240514</enddate><creator>Han, Yue</creator><creator>Li, Min</creator><creator>Zhao, Bingqing</creator><creator>Wang, Huichao</creator><creator>Liu, Yan</creator><creator>Liu, Zhijun</creator><creator>Xu, Jiaxi</creator><creator>Yang, Rui</creator><general>National Academy of Sciences</general><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>7QR</scope><scope>7SN</scope><scope>7SS</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>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0009-0006-4661-0682</orcidid><orcidid>https://orcid.org/0009-0002-9481-4322</orcidid><orcidid>https://orcid.org/0009-0003-3731-840X</orcidid><orcidid>https://orcid.org/0009-0003-5170-6476</orcidid><orcidid>https://orcid.org/0000-0003-1006-7893</orcidid></search><sort><creationdate>20240514</creationdate><title>MARK2 phosphorylates KIF13A at a 14-3-3 binding site to polarize vesicular transport of transferrin receptor within dendrites</title><author>Han, Yue ; Li, Min ; Zhao, Bingqing ; Wang, Huichao ; Liu, Yan ; Liu, Zhijun ; Xu, Jiaxi ; Yang, Rui</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c335t-1e7b9f2cbca1a559fc3c42e2158351e9fa0e202b0ee9afacb725f2d4cb461d2b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>14-3-3 protein</topic><topic>14-3-3 Proteins - metabolism</topic><topic>Animals</topic><topic>Anterograde transport</topic><topic>Axonal transport</topic><topic>Axons</topic><topic>Binding Sites</topic><topic>Biological Sciences</topic><topic>Dendrites</topic><topic>Dendrites - metabolism</topic><topic>Humans</topic><topic>Kinases</topic><topic>Kinesin</topic><topic>Kinesins - genetics</topic><topic>Kinesins - metabolism</topic><topic>Mice</topic><topic>Microtubules</topic><topic>Microtubules - metabolism</topic><topic>Phosphorylation</topic><topic>Protein Binding</topic><topic>Protein Serine-Threonine Kinases - genetics</topic><topic>Protein Serine-Threonine Kinases - metabolism</topic><topic>Protein-serine/threonine kinase</topic><topic>Rats</topic><topic>Receptors</topic><topic>Receptors, Transferrin - metabolism</topic><topic>Transferrin</topic><topic>Transferrins</topic><topic>Vesicles</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Han, Yue</creatorcontrib><creatorcontrib>Li, Min</creatorcontrib><creatorcontrib>Zhao, Bingqing</creatorcontrib><creatorcontrib>Wang, Huichao</creatorcontrib><creatorcontrib>Liu, Yan</creatorcontrib><creatorcontrib>Liu, Zhijun</creatorcontrib><creatorcontrib>Xu, Jiaxi</creatorcontrib><creatorcontrib>Yang, Rui</creatorcontrib><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>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</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>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>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Han, Yue</au><au>Li, Min</au><au>Zhao, Bingqing</au><au>Wang, Huichao</au><au>Liu, Yan</au><au>Liu, Zhijun</au><au>Xu, Jiaxi</au><au>Yang, Rui</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MARK2 phosphorylates KIF13A at a 14-3-3 binding site to polarize vesicular transport of transferrin receptor within dendrites</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2024-05-14</date><risdate>2024</risdate><volume>121</volume><issue>20</issue><spage>e2316266121</spage><pages>e2316266121-</pages><issn>0027-8424</issn><issn>1091-6490</issn><eissn>1091-6490</eissn><abstract>Neurons regulate the microtubule-based transport of certain vesicles selectively into axons or dendrites to ensure proper polarization of function. The mechanism of this polarized vesicle transport is still not fully elucidated, though it is known to involve kinesins, which drive anterograde transport on microtubules. Here, we explore how the kinesin-3 family member KIF13A is regulated such that vesicles containing transferrin receptor (TfR) travel only to dendrites. In experiments involving live-cell imaging, knockout of KIF13A, BioID assay, we found that the kinase MARK2 phosphorylates KIF13A at a 14-3-3 binding motif, strengthening interaction of KIF13A with 14-3-3 such that it dissociates from TfR-containing vesicles, which therefore cannot enter axons. Overexpression of KIF13A or knockout of MARK2 leads to axonal transport of TfR-containing vesicles. These results suggest a unique kinesin-based mechanism for polarized transport of vesicles to dendrites.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>38709923</pmid><doi>10.1073/pnas.2316266121</doi><orcidid>https://orcid.org/0009-0006-4661-0682</orcidid><orcidid>https://orcid.org/0009-0002-9481-4322</orcidid><orcidid>https://orcid.org/0009-0003-3731-840X</orcidid><orcidid>https://orcid.org/0009-0003-5170-6476</orcidid><orcidid>https://orcid.org/0000-0003-1006-7893</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0027-8424 |
| ispartof | Proceedings of the National Academy of Sciences - PNAS, 2024-05, Vol.121 (20), p.e2316266121 |
| issn | 0027-8424 1091-6490 1091-6490 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11098127 |
| source | MEDLINE; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | 14-3-3 protein 14-3-3 Proteins - metabolism Animals Anterograde transport Axonal transport Axons Binding Sites Biological Sciences Dendrites Dendrites - metabolism Humans Kinases Kinesin Kinesins - genetics Kinesins - metabolism Mice Microtubules Microtubules - metabolism Phosphorylation Protein Binding Protein Serine-Threonine Kinases - genetics Protein Serine-Threonine Kinases - metabolism Protein-serine/threonine kinase Rats Receptors Receptors, Transferrin - metabolism Transferrin Transferrins Vesicles |
| title | MARK2 phosphorylates KIF13A at a 14-3-3 binding site to polarize vesicular transport of transferrin receptor within dendrites |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-11T12%3A12%3A44IST&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=MARK2%20phosphorylates%20KIF13A%20at%20a%2014-3-3%20binding%20site%20to%20polarize%20vesicular%20transport%20of%20transferrin%20receptor%20within%20dendrites&rft.jtitle=Proceedings%20of%20the%20National%20Academy%20of%20Sciences%20-%20PNAS&rft.au=Han,%20Yue&rft.date=2024-05-14&rft.volume=121&rft.issue=20&rft.spage=e2316266121&rft.pages=e2316266121-&rft.issn=0027-8424&rft.eissn=1091-6490&rft_id=info:doi/10.1073/pnas.2316266121&rft_dat=%3Cproquest_pubme%3E3051939726%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=3058864139&rft_id=info:pmid/38709923&rfr_iscdi=true |