Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 105, Issue 44, Pages 17181-17186Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0800846105
Keywords
BDNF; dendrite; neuronal activity; Rac; prenylation
Categories
Funding
- National Natural Science Foundation of China [30721004, 30825013]
- 973 Program and Key State Research Program of China [2006CB806600, 2006CB943900]
- Chinese Academy of Sciences [KSCX2-YW-R-102]
- Program of Shanghai Subject Chief Scientist [08XD14050]
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Dendrite morphogenesis is regulated by neuronal activity or neurotrophins, which may function by activating intrinsic signaling proteins, including Rho family GTPases. Here we report that activity- and brain-derived neurotrophic factor (BDNF)- dependent dendritic morphogenesis requires activation of geranylgeranyltransferase I (GGT), a prenyltransferase that mediates lipid modification of Rho GTPases. Dendritic arborization in cultured hippocampal neurons was promoted by over-expression of GGT, and reduced by inhibition or down-regulation of GGT. Furthermore, GGT was activated by neuronal depolarization or BDNF, both of which promote dendritic arborization, in cultured hippocampal neurons. Moreover, exploration of a novel environment caused activation of GGT in the mice hippocampus, suggesting that neural activity activates GGT in vivo. Interestingly, GGT was physically associated with tropomyosin-related kinase B (TrkB), the receptor for BDNF, and this association was enhanced by depolarization. Disrupting the GGT-TrkB interaction or down-regulating GGT activity attenuated depolarization- or BDNF-induced dendrite development. Finally, the GGT effect on dendrite arborization was prevented by over-expressing Rac1 with the prenylation site deleted or mutated. Thus depolarization- or BDNF-dependent dendrite development may be mediated by GGT-induced prenylation of Rho GTPases.
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