Autor: |
Sangmook Lee, Thomas B. Shea |
Jazyk: |
angličtina |
Rok vydání: |
2014 |
Předmět: |
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Zdroj: |
Biology Open, Vol 3, Iss 10, Pp 974-981 (2014) |
Druh dokumentu: |
article |
ISSN: |
2046-6390 |
DOI: |
10.1242/bio.20149779 |
Popis: |
Neurofilaments (NFs) are thought to provide structural support to mature axons via crosslinking of cytoskeletal elements mediated by the C-terminal region of the high molecular weight NF subunit (NF-H). Herein, we inhibited NF-H expression in differentiating mouse NB2a/d1 cells with shRNA directed against murine NF-H without affecting other NF subunits, microtubules or actin. shRNA-mediated NF-H knockdown not only in compromised of late-stage axonal neurite stabilization but also compromised early stages of axonal neurite elongation. Expression of exogenous rat NF-H was able to compensate for knockdown of endogenous NF-H and restored the development and stabilization of axonal neurites. This rescue was prevented by simultaneous treatment with shRNA that inhibited both rat and murine NF-H, or by expression of exogenous rat NF-H lacking the C-terminal sidearm during knockdown of endogenous NF-H. Demonstration of a role for NF-H in the early stages of axonal elaboration suggests that axonal stabilization is not delayed until synaptogenesis, but rather that the developing axon undergoes sequential NF-H-mediated stabilization along its length in a proximal–distal manner, which supports continued pathfinding in distal, unstabilized regions. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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