On Oct. 28, PNAS published online a paper from ION entitled "TrkB-mediated Activation of Geranylgeranyltransferase I Promotes Dendritic Morphogenesis". This work was mainly done by graduate student Xiu-Ping Zhou, under the supervision of Dr. Zhen-Ge Luo.

Dendrite morphogenesis is regulated by neuronal activity or neurotrophins, which may function by activating intrinsic signaling proteins, including Rho family GTPases. Zhou et al. report that activity- and brain-derived neurotrophic factor (BDNF)-dependent dendritic morphogenesis requires activation of geranylgeranyltransferase I (GGT), a prenyltransferase which mediates lipid modification of Rho GTPases. They found that 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. Exploration of a novel environment caused activation of GGT in the mouse hippocampus, suggesting that neural activity activates GGT in vivo. Interestingly, GGT is 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. Together, these observations reveal the critical role of GGT in dendrite development, and the mechanism by which GGT is regulated in central neurons.