Geranylgeranyltransferase I mediates BDNF-induced synaptogenesis.

Area of Science:

• Neuroscience
• Molecular Biology
• Cell Biology

Background:

• Geranylgeranyltransferase I (GGT) is a prenyltransferase involved in lipid modification of Rho GTPases.
• Rho GTPases like Rac and Cdc42 are essential for neuronal synaptogenesis.
• The precise function of GGT in the central nervous system, particularly in synaptogenesis, remains largely uncharacterized.

Purpose of the Study:

• To investigate the role and underlying mechanism of GGT in neuronal synaptogenesis.
• To explore the relationship between GGT, BDNF signaling, and synapse formation.

Main Methods:

• Analysis of GGT protein level and activity in rat hippocampus during development (P7-P28).
• Investigation of GGT subcellular localization in neuronal synapses.
• Manipulation of GGT expression (over-expression, inhibition, down-regulation) and its effect on synaptic proteins (Synapsin 1, PSD-95).
• Assessment of Rac1 activation by BDNF and its role in GGT-mediated synaptogenesis.

Main Results:

• GGT protein levels and activity increase in the hippocampus from P7 to P28 and localize to neuronal synapses.
• GGT over-expression enhances Synapsin 1 and PSD-95 density, while GGT inhibition/down-regulation reduces them.
• BDNF activates GGT and its substrate Rac1, promoting synaptogenesis; this effect is blocked by GGT inhibition or non-prenylated Rac1.

Conclusions:

• GGT plays a significant role in neuronal synaptogenesis.
• GGT mediates BDNF-induced synaptogenesis through the activation of Rac1.
• These findings highlight GGT as a key regulator in synaptic development and plasticity.