日本奈良尖端科學技術(shù)大學院大學,、東北大學等機構(gòu)的研究人員12日報告說,他們通過動物實驗,,發(fā)現(xiàn)了神經(jīng)細胞軸突形成的機制,。
軸突是神經(jīng)細胞長出的一根較長的圓柱形細長突起,,每個正常的神經(jīng)細胞只會伸出一個軸突。它是神經(jīng)系統(tǒng)主要的信號傳遞通道,,人類的軸突最長可以達到1米,。
此前,研究人員已知軸突的前端是通過擴展細胞膜而伸長的,,但是一直不清楚其詳細的形成機制,。新研究中,奈良尖端科學技術(shù)大學院大學副教授稻垣直之等人利用大鼠腦神經(jīng)細胞進行實驗,,發(fā)現(xiàn)細胞內(nèi)的一種蛋白質(zhì)“Rab33a”會將合成細胞膜的成分運到軸突前端,,從而使軸突向前生長。
研究人員還發(fā)現(xiàn),,如果減少“Rab33a”蛋白質(zhì)的量,,軸突形成就減緩,如果這種蛋白質(zhì)過量,,則細胞膜成分的供應(yīng)過剩,,一個神經(jīng)細胞會長出多條軸突。
這一研究成果已發(fā)表在新一期《神經(jīng)科學雜志》上,。稻垣直之認為,,新發(fā)現(xiàn)將有助于治療脊髓損傷等疾病,在再生醫(yī)療領(lǐng)域得到應(yīng)用,。(生物谷Bioon.com)
doi: 10.1523/JNEUROSCI.0989-12.2012
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Rab33a Mediates Anterograde Vesicular Transport for Membrane Exocytosis and Axon Outgrowth
Hitomi Nakazawa, Tadayuki Sada, Michinori Toriyama, Kenji Tago, Tadao Sugiura, Mitsunori Fukuda, and Naoyuki Inagaki
Axon outgrowth requires plasma membrane expansion, which results from post-Golgi vesicular transport and fusion. However, the molecular mechanisms regulating post-Golgi vesicular trafficking for membrane expansion and axon outgrowth remain unclear. Here, we show that Rab33a expression became upregulated during axon outgrowth of cultured rat hippocampal neurons. Rab33a was preferentially localized to the Golgi apparatus and to synaptophysin-positive vesicles that are transported along the growing axon. Previous studies showed that synaptophysin is localized to post-Golgi vesicles transported by fast axonal transport in developing neurons. Reduction of Rab33a expression by RNAi (RNA interference) inhibited the anterograde transport of synaptophysin-positive vesicles, leading to their decrease in axonal tips. Furthermore, this treatment reduced membrane fusion of synaptophysin-positive vesicles at the growth cones and inhibited axon outgrowth. Overexpression of Rab33a, on the other hand, induced excessive accumulation of synaptophysin-positive vesicles and concurrent formation of surplus axons. These data suggest that Rab33a participates in axon outgrowth by mediating anterograde axonal transport of synaptophysin-positive vesicles and their concomitant fusion at the growth cones.