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dc.contributor.authorKerman, Bilal Ersen
dc.contributor.authorGenoud, Stephane
dc.contributor.authorKurt Vatandaşlar, Burcu
dc.contributor.authorDenli, Ahmet Murat
dc.contributor.authorGhosh, Shereen Georges
dc.contributor.authorXu, Xiangdong
dc.contributor.authorYeo, Gene W.
dc.contributor.authorAimone, James Bradley
dc.contributor.authorGage, Fred H.
dc.date.accessioned2020-09-28T10:52:34Z
dc.date.available2020-09-28T10:52:34Z
dc.date.issued2020en_US
dc.identifier.citationKerman, B. E., Genoud, S., Kurt Vatandaşlar, B., Denli, A. M., Ghosh, S. G., Xu, X. ... Gage, F. H. (2020). Motoneuron expression profiling identifies an association between an axonal splice variant of HDGF-related protein 3 and peripheral myelination. Journal of Biological Chemistry, 295(34), 12233-12246. https://dx.doi.org/10.1074/jbc.RA120.014329en_US
dc.identifier.issn0021-9258
dc.identifier.issn1083-351X
dc.identifier.urihttps://dx.doi.org/10.1074/jbc.RA120.014329
dc.identifier.urihttps://hdl.handle.net/20.500.12511/5876
dc.description.abstractDisorders that disrupt myelin formation during development or in adulthood, such as multiple sclerosis and peripheral neuropathies, lead to severe pathologies, illustrating myelin's crucial role in normal neural functioning. However, although our understanding of glial biology is increasing, the signals that emanate from axons and regulate myelination remain largely unknown. To identify the core components of the myelination process, here we adopted a microarray analysis approach combined with laser-capture microdissection of spinal motoneurons during the myelinogenic phase of development. We identified neuronal genes whose expression was enriched during myelination and further investigated hepatoma-derived growth factor-related protein 3 (HRP3 or HDGFRP3). HRP3 was strongly expressed in the white matter fiber tracts of the peripheral (PNS) and central (CNS) nervous systems during myelination and remyelination in a cuprizone-induced demyelination model. The dynamic localization of HPR3 between axons and nuclei during myelination was consistent with its axonal localization during neuritogenesis. To study this phenomenon, we identified two splice variants encoded by theHRP3gene: the canonical isoform HRP3-I and a newly recognized isoform, HRP3-II. HRP3-I remained solely in the nucleus, whereas HRP3-II displayed distinct axonal localization both before and during myelination. Interestingly, HRP3-II remained in the nuclei of unmyelinated neurons and glial cells, suggesting the existence of a molecular machinery that transfers it to and retains it in the axons of neurons fated for myelination. Overexpression of HRP3-II, but not of HRP3-I, increased Schwann cell numbers and myelination in PNS neuron-glia co-cultures. However, HRP3-II overexpression in CNS co-cultures did not alter myelination.en_US
dc.description.sponsorshipChristopher and Dana Reeve Foundation Roche Foundation Swiss National Science Foundation (SNSF) American Heart Association Paul G. Allen Frontiers Group Grant Leona M. and Harry B. Helmsley Charitable Trust Grant Grace Foundation JPB Foundation Robert and Mary Jane Engman Foundation Ray and Dagmar Dolby Family Fund Crick-Jacob Center for Theoretical and Computational Biology Neurosurgery Neuroscience Consortium Fellowshipen_US
dc.language.isoengen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biology Incen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectMyelinen_US
dc.subjectOligodendrocyteen_US
dc.subjectSchwann Cellsen_US
dc.subjectAlternative Splicingen_US
dc.subjectNuclear Translocationen_US
dc.subjectSpinal Motoneuronen_US
dc.subjectHepatoma-Derived Growth Factor-Related Protein 3 (HRP3)en_US
dc.subjectHDGFRP3en_US
dc.subjectAxonen_US
dc.subjectNeuritogenesisen_US
dc.titleMotoneuron expression profiling identifies an association between an axonal splice variant of HDGF-related protein 3 and peripheral myelinationen_US
dc.typearticleen_US
dc.relation.ispartofJournal of Biological Chemistryen_US
dc.departmentİstanbul Medipol Üniversitesi, Uluslararası Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Histoloji ve Embriyoloji Ana Bilim Dalıen_US
dc.departmentİstanbul Medipol Üniversitesi, Rektörlük, Rejeneratif ve Restoratif Tıp Araştırmaları Merkezi (REMER)en_US
dc.departmentİstanbul Medipol Üniversitesi, Sağlık Bilimleri Enstitüsü, Sinirbilim Ana Bilim Dalıen_US
dc.authorid0000-0003-1106-3288en_US
dc.identifier.volume295en_US
dc.identifier.issue34en_US
dc.identifier.startpage12233en_US
dc.identifier.endpage12246en_US
dc.relation.tubitakinfo:eu-repo/grantAgreement/TUBITAK/SOBAG/116S059
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.identifier.doi10.1074/jbc.RA120.014329en_US
dc.identifier.wosqualityQ2en_US
dc.identifier.scopusqualityQ1en_US


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