The kinesin motor KIF11 coordinates NLR localization and activation in the innate immune response

The kinesin motor KIF11 coordinates NLR localization and activation in the innate immune response | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article The kinesin motor KIF11 coordinates NLR localization and activation in the innate immune response Takeshi Kinoshita, Kohsuke Tsuchiya, Daisuke Inoue, Shinsuke Nakajima, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8293641/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) detect invading pathogens and danger-associated signals, but how their intracellular localization is controlled remains unclear. Through a genome-wide shRNA screen, we identified the kinesin-related motor protein KIF11 as a critical component of NLRC4-dependent innate immune responses. KIF11 interacts with the NOD of NLRC4, NLRP3, and NOD2 via its motor domain, and its inhibition attenuates these NLR-mediated immune responses. In vitro reconstitution assays revealed that KIF11 binds to and transports NLRs along microtubules, while immunocytochemical analyses showed their colocalization under resting conditions. KIF11 inhibition decreased the levels of microtubule-associated NLRs within their respective intracellular compartments. These findings uncover KIF11 as a common upstream component that orchestrates pre-stimulation NLR positioning and subsequent activation, providing a mechanistic link between cytoskeletal dynamics and innate immune signaling. Biological sciences/Immunology/Innate immunity/Pattern recognition receptors/NOD-like receptors Biological sciences/Cell biology/Protein transport/Protein translocation Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplTable1Module1.xlsx Supplementary Table 1 Candidate genes identified from the module 1 shRNA library screening. SupplTable4Top10.xlsx Supplementary Table 4 Top 10 candidate genes based on maximum z-scores of enriched shRNAs. SupplementaryMov3.mp4 Supplementary Mov. 3 rssss.pdf Reporting Summary SupplementaryMov2.mp4 Supplementary Mov. 2 Source.xlsx Source Data SupplementaryMov1.mp4 Supplementary Mov. 1 SupplTable2Module2.xlsx Supplementary Table 2 Candidate genes identified from the module 2 shRNA library screening. SupplTable3Module3.xlsx Supplementary Table 3 Candidate genes identified from the module 3 shRNA library screening. Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8293641","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":569765387,"identity":"345f3e01-e7e0-4284-a2cf-4285babd4d79","order_by":0,"name":"Takeshi 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response","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"nature-portfolio","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"","title":"Nature Portfolio","twitterHandle":"","acdcEnabled":false,"dfaEnabled":false,"editorialSystem":"ejp","reportingPortfolio":"","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-8293641/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8293641/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) detect invading pathogens and danger-associated signals, but how their intracellular localization is controlled remains unclear. Through a genome-wide shRNA screen, we identified the kinesin-related motor protein KIF11 as a critical component of NLRC4-dependent innate immune responses. KIF11 interacts with the NOD of NLRC4, NLRP3, and NOD2 via its motor domain, and its inhibition attenuates these NLR-mediated immune responses. In vitro reconstitution assays revealed that KIF11 binds to and transports NLRs along microtubules, while immunocytochemical analyses showed their colocalization under resting conditions. KIF11 inhibition decreased the levels of microtubule-associated NLRs within their respective intracellular compartments. These findings uncover KIF11 as a common upstream component that orchestrates pre-stimulation NLR positioning and subsequent activation, providing a mechanistic link between cytoskeletal dynamics and innate immune signaling.","manuscriptTitle":"The kinesin motor KIF11 coordinates NLR localization and activation in the innate immune response","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-06 11:32:43","doi":"10.21203/rs.3.rs-8293641/v1","editorialEvents":[],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"communications-biology","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"commsbio","sideBox":"Learn more about [Communications Biology](http://www.nature.com/commsbio/)","snPcode":"","submissionUrl":"","title":"Communications Biology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Communications Series","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"10b6b993-b601-4ee0-98c1-fb374e490e0d","owner":[],"postedDate":"January 6th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":60625296,"name":"Biological sciences/Immunology/Innate immunity/Pattern recognition receptors/NOD-like receptors"},{"id":60625297,"name":"Biological sciences/Cell biology/Protein transport/Protein translocation"}],"tags":[],"updatedAt":"2026-01-26T10:52:06+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-06 11:32:43","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8293641","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8293641","identity":"rs-8293641","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}