2011
DOI: 10.1007/s00018-010-0616-z
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From axon–glial signalling to myelination: the integrating role of oligodendroglial Fyn kinase

Abstract: Central nervous system myelination requires recognition and signalling processes between neuronal axons and oligodendrocytes. Complex cellular rearrangements occur in myelination-competent oligodendrocytes requiring spatio-temporal control mechanisms. Although the molecular repertoire is becoming increasingly transparent, the signalling mechanisms governing myelination initiation are only poorly understood. The non-receptor tyrosine kinase Fyn has been implicated in axon-glial signal transduction and in severa… Show more

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Cited by 107 publications
(121 citation statements)
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“…Taken in isolation, this result is consistent with in vitro studies documenting that Contactin on oligodendrocytes promotes myelin membrane generation (18). The proposed model is that engagement of glial Contactin activates Src-related intracellular kinase Fyn to induce transport and local translation of MBP mRNA at oligodendrocyte processes increasing membrane expansion (18,29). Consistent with this model, Cntn1-KO mice show hypomyelination and overall MBP reduction in multiple myelinated areas of the CNS, similar to the phenotype in Fyndeficient mice (30).…”
Section: Contactin In Axon-glia Interactions Initiating Myelin Formatsupporting
confidence: 83%
“…Taken in isolation, this result is consistent with in vitro studies documenting that Contactin on oligodendrocytes promotes myelin membrane generation (18). The proposed model is that engagement of glial Contactin activates Src-related intracellular kinase Fyn to induce transport and local translation of MBP mRNA at oligodendrocyte processes increasing membrane expansion (18,29). Consistent with this model, Cntn1-KO mice show hypomyelination and overall MBP reduction in multiple myelinated areas of the CNS, similar to the phenotype in Fyndeficient mice (30).…”
Section: Contactin In Axon-glia Interactions Initiating Myelin Formatsupporting
confidence: 83%
“…Furthermore, supporting the involvement of Tau and other cytoskeletal elements in myelination process, previous evidence suggests that Tau strongly colocalizes with MBP in distal tips of oligodendrocytes (LoPresti et al ., 1995; Muller et al ., 1997), suggesting that transportation and/or local MBP translation may require microtubule cytoskeleton and might be controlled by Tau–Fyn interaction (Klein et al ., 2002). As recent evidence suggests that Tau is responsible to locate Fyn in spines and Fyn has a well‐described role in myelination of both CNS and PNS (Kramer‐Albers & White, 2011), the above Tau–Fyn–MBP complex could be disrupted in the absence of Tau protein, affecting myelination signaling and process. Indeed, Taiep myelin‐mutant animals exhibit irregular microtubule polarity and display abnormal Tau accumulation and intracellular accumulation of myelin proteins in oligodendrocytes (Song et al ., 2001), while PNS myelin‐deficient mice also exhibited reduction in Tau and other cytoskeletal protein in their sciatic nerves (Kirkpatrick & Brady, 1994).…”
Section: Discussionmentioning
confidence: 99%
“…MBP compacts the forming myelin sheaths but may indeed have additional roles in the oligodendrocyte (8 -10). Activation of the Src family nonreceptor tyrosine kinase Fyn is instrumental for oligodendrocyte differentiation and myelination (11)(12)(13)(14); Fyn mutant mice are hypomyelinated, and MBP levels are reduced (15)(16)(17).…”
Section: Myelin Basic Protein (Mbp) Ismentioning
confidence: 99%