کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4323956 1613841 2015 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Semaphorin3A-induced axonal transport mediated through phosphorylation of Axin-1 by GSK3β
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
Semaphorin3A-induced axonal transport mediated through phosphorylation of Axin-1 by GSK3β
چکیده انگلیسی


• GSK3β is necessary for Sema3A signaling that accelerates axonal transport.
• The phosphorylation of unprimed substrates is required for the Sema3A signaling.
• Axin-1 is an unprimed substrate that mediates Sema3A-induced axonal transport.
• GSK3β-Axin-1 signaling plays important roles in Sema3A signaling.

The establishment of neuronal polarity is necessary for proper neuronal wiring. Semaphorin3A (Sema3A), originally identified as a repulsive axon guidance molecule, exerts a wide variety of biological functions through signaling pathways including sequential phosphorylation of collapsin response mediator protein by cyclin-dependent kinase-5 (Cdk5) and glycogen synthase kinase-3β (GSK3β). Sema3A acts on its receptor neuropilin-1 to regulate axonal transport. To delineate mechanism by which Sema3A induces axonal transport, we investigate whether GSK3β is involved in mediating Sema3A-induced axonal transport. 4-Benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione, an inhibitor of GSK3β, suppressed Sema3A-induced antero- and retrograde axonal transport. Introduction of either GSK3β mutants, GSK3β-L128A or K85M, suppressed Sema3A-induced axonal transport. On the other hand, introduction of GSK3β-R96A did not affect the Sema3A effect, suggesting that unprimed substrates are primarily involved in Sema3A-induced axonal transport. Overexpression of a partial fragment of frequently rearranged in advanced T-cell lymphomas 1 (FRATtide), which interferes the interaction between GSK3β and Axis inhibitor-1 (Axin-1), also suppressed Sema3A-induced transport. siRNA knockdown of Axin-1, an unprimed substrate of GSK3β, suppressed Sema3A-induced antero- and retrograde axonal transport. These results indicate that GSK3β and Axin-1 are involved in Sema3A-induced bidirectional axonal transport. This finding should provide a clue for understanding of mechanisms of a wide variety of biological activities of Sema3A.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Brain Research - Volume 1598, 19 February 2015, Pages 46–56
نویسندگان
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