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This study demonstrates that the multi-tRNA synthetase complex (MSC) specifically interacts with KTN1 in a manner dependent on the alternative exon V2 and glutamine-tRNA synthetase (QARS). V2 exon-specific and KTN1 knockout cells with variant-specific rescue show that V2 is required for KTN1-mediated MSC recruitment to the ER. This recruitment enables formation of rough ER stacks and reveals a noncanonical MSC role in regulating ER sheet organization.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/variant-specific-interaction-of-kinectin-1-with-the-multi-trna-synthetase-complex-regulates-er-sheet-organization/440763/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/variant-specific-interaction-of-kinectin-1-with-the-multi-trna-synthetase-complex-regulates-er-sheet-organization/440763.png","ImageObject",300,407,{"name":92,"@type":93},"Logic","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-02","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":81},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the key finding about kinectin 1 (KTN1) variants?","Question",{"text":112,"@type":113},"The study shows that KTN1 variants act in a way that depends on the alternative exon V2, enabling a specific interaction with the multi-tRNA synthetase complex.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does the multi-tRNA synthetase complex (MSC) relate to the ER?",{"text":117,"@type":113},"MSC is recruited to the ER through a V2- and QARS-dependent interaction with KTN1, where it promotes formation of rough ER stacks.",{"name":119,"@type":110,"acceptedAnswer":120},"Which experimental approach established that V2 is required?",{"text":121,"@type":113},"The authors used V2 exon-specific knockout cells and KTN1 knockout cells with variant-specific rescue, demonstrating that the V2 exon is necessary for KTN1-mediated MSC recruitment to the ER.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},440763,1790813716,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":81,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},1099513958762,"https://ap-avatar.wpscdn.com/avatar/1000023916a998db790?x-image-process=image/resize,m_fixed,w_180,h_180&k=1784791008015729253","iScience Article  \nVariant-specific interaction of kinectin 1 with the multi-tRNA synthetase complex regulates ER sheet organization  \nAuthors  \nMasaki Hosogane, Sue-yi Siao, Atsushi Hatano,   , Shintaro Iwasaki, Masaki Matsumoto, Keiko Nakayama  \nCorrespondence  \n[m-hosogane@dokkyomed.ac.jp](m-hosogane@dokkyomed.ac.jp) (M.H.),  \n[keiko.nakayama.e4@tohoku.ac.jp](keiko.nakayama.e4@tohoku.ac.jp) (K.N.)  \nIn brief  \nBiochemistry; Molecular biology; Cell biology  \n• The V2-encoded region binds to the N-terminal domain of QARS within the MSC  \n• This binding is essential for MSC relocation to the endoplasmic reticulum (ER)  \n• MSC relocation by KTN1 induces the formation of ER stacks  \nHosogane et al., 2026, iScience 29, 114303  \nJanuary 16, 2026 © 2025 The Authors. Published by Elsevier Inc.  \n[https://doi.org/10.1016/j.isci.2025.114303](https://doi.org/10.1016/j.isci.2025.114303)  \nll  \niScience  \nll  \nOPEN ACCESS  \nArticle  \nVariant-specific interaction of kinectin 1 with the multi-tRNA synthetase complex regulates ER sheet organization  \nMasaki Hosogane,1,2,9,* Sue-yi Siao,1 Atsushi Hatano,3 Xiaoxin Huang,1 Yuichi Shichino,4,5 Yasuaki Watanabe,1,6 Shintaro Iwasaki,4,7 Masaki Matsumoto,3 and Keiko Nakayama1,8,*  \n1Division of Cell Proliferation, ART, Graduate School of Medicine, Tohoku University, Sendai, Miyagi 980-8575, Japan  \n2Department of Medical Genome Science, Dokkyo Medical University, Mibu, Tochigi 321-0293, Japan  \n3Department of Omics and Systems Biology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan  \n4RNA Systems Biochemistry Laboratory, Pioneering Research Institute, RIKEN, Wako, Saitama 351-0198, Japan  \n5Department of RNA Biochemistry, Institute of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan  \n6Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8575, Japan  \n7Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba 277-8561, Japan  \n8National Institutes for Quantum Science and Technology, Chiba, Chiba 263-8555, Japan  \n9Lead contact  \n*[Correspondence:](Correspondence: m-hosogane@dokkyomed.ac.jp)[ m-hosogane@dokkyomed.ac.jp](Correspondence: m-hosogane@dokkyomed.ac.jp) (M. H.), [keiko.nakayama.e4@tohoku.ac.jp](keiko.nakayama.e4@tohoku.ac.jp) (K. N.) [https://doi.org/10.1016/j.isci.2025.114303](https://doi.org/10.1016/j.isci.2025.114303)  \nSUMMARY  \nKinectin 1 (KTN1) is an integral endoplasmic reticulum (ER) sheet protein involved in ER organization and translation elongation. Alternative splicing introduces sequence diversity into the cytosolic region of KTN1; however, the functional significance of these variants has remained unclear. Here, we show that the multi-tRNA synthetase complex (MSC), composed of eight aminoacyl-tRNA synthetases and three nonenzymatic proteins, specifically interacts with KTN1 in a manner dependent on the alternative exon V2 and glutamine-tRNA synthetase (QARS) . Using V2 exon-specific knockout cells and KTN1 knockout cells with variantspecific rescue, we found that the V2 exon is required for KTN1-mediated recruitment of the MSC to the ER, where it facilitates the formation of rough ER stacks. These findings define a variant-specific role for KTN1 in anchoring the MSC to the ER and suggest that this interaction underlies a noncanonical function of the MSC in regulating ER sheet organization.  \nINTRODUCTION  \nThe endoplasmic reticulum (ER) is a continuous membrane network consisting of interconnected tubules and cisternal sheets, the latter of which are associated with ribosomes engaged in the synthesis of secreted or membrane proteins.1 ,2 Proteins enriched at the ER membrane regulate organization of the ER, including its shape and distribution.3 ,4 These proteins include integral coiled-coil proteins such as CLIMP63, RRBP1, and kinectin 1 (KTN1) .1 The N-terminal domain of KTN1 anchors the protein to ","cbCaiavtpztEoybW","https://ap.wps.com/l/cbCaiavtpztEoybW","pdf",14444477,26,"English","# Summary\n# Introduction\n# Results\n## V2 exon-dependent MSC recruitment to the ER\n## KTN1-mediated ER rough stack formation\n# Discussion","[{\"question\":\"What is the key finding about kinectin 1 (KTN1) variants?\",\"answer\":\"The study shows that KTN1 variants act in a way that depends on the alternative exon V2, enabling a specific interaction with the multi-tRNA synthetase complex.\"},{\"question\":\"How does the multi-tRNA synthetase complex (MSC) relate to the ER?\",\"answer\":\"MSC is recruited to the ER through a V2- and QARS-dependent interaction with KTN1, where it promotes formation of rough ER stacks.\"},{\"question\":\"Which experimental approach established that V2 is required?\",\"answer\":\"The authors used V2 exon-specific knockout cells and KTN1 knockout cells with variant-specific rescue, demonstrating that the V2 exon is necessary for KTN1-mediated MSC recruitment to the ER.\"}]","Variant-specific interaction of kinectin 1 with the multi-tRNA synthetase complex regulates ER sheet organization | PDF",1790693279,66]