Cholesterol-dependent modulation of dendrite outgrowth and microtubule stability in cultured neurons

Qi Wen Fan, Wei Yu, Jian Sheng Gong, Kun Zou, Naoya Sawamura, Takao Senda, Katsuhiko Yanagisawa, Makoto Michikawa*

*この研究の対応する著者

研究成果: Article査読

98 被引用数 (Scopus)

抄録

Microtubule-associated protein 2 (MAP2) is a neuron-specific cytoskeletal protein enriched in dendrites and cell bodies. MAP2 regulates microtubule stability in a phosphorylation-dependent manner, which has been implicated in dendrite outgrowth and branching. We have previously reported that cholesterol deficiency causes tau phosphorylation and microtubule depolymerization in axons (Fan et al. 2001). To investigate whether cholesterol also modulates microtubule stability in dendrites by modulating MAP2 phosphorylation, we examined the effect of compactin, a 3-hydroxy-3-methylglut-aryl coenzyme A (HMG-CoA) reductase inhibitor, and TU-2078 (TU), a squalene epoxidase inhibitor, on these parameters using cultured neurons. We have found that cholesterol deficiency induced by compactin and TU, inhibited dendrite outgrowth, but not of axons, and attenuated axonal branching. Dephosphorylation of MAP2 and microtubule depolymerization accompanied these alterations. The amount of protein phosphatase 2 A (PP2A) and its activity in association with microtubules were decreased, while those unbound to microtubules were increased. The synthesized ceramide levels and the total ceramide content were increased in these cholesterol-deficient neurons. These alterations caused by compactin were prevented by concurrent treatment of cultured neurons with β-migrating very-low-density lipoproteins (β-VLDL) or cholesterol. Taken together, we propose that cholesterol-deficiency causes a selective inhibition of dendrite outgrowth due to the decreased stability of microtubules as a result of inhibition of MAP2 phosphorylation.

本文言語English
ページ(範囲)178-190
ページ数13
ジャーナルJournal of neurochemistry
80
1
DOI
出版ステータスPublished - 2002
外部発表はい

ASJC Scopus subject areas

  • 生化学
  • 細胞および分子神経科学

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