New Modes of GPCR Signalling

GABAB Receptor-Mediated Rap1 Activation and GB1/Rap1GTP
Interaction in Neuronal System
Zongyong Zhang, Siluo Huang,Ninghua Sun,Lin Wu,Yilei Zhang,Jianfeng Liu, Li Su
Sino-France Laboratory for Drug Screening, Key Laboratory of Molecular Biophysics of
Ministry of Education, School of Life Science and Technology, Huazhong University of
Science and Technology, Wuhan, 430074 ,China
Rap1, a Ras-related small GTPase, binds to either GTP(Rap1GTP active form ) or GDP
(Rap1GDP inactive form) to regulate cell proliferation, adhesion, or migration.
Gamma-aminobutyric acid (GABA) B receptors, which are GB1/GB2 heterodimer, play
an important role in many physiological activities in neuron. We found that activation
of GABAB receptor stimulated with Baclofen or CGP7930, analogs of GABA, activated
Rap1 signaling both in cultured mice cerebellar granule neurons (CGNs) and in
HEK293 cell. This activation can be blocked by depleting of Ca 2+ in the medium with
Ca 2+ chelator BAPTA. We further found the active Rap1 translocated to premembrane
region and interacted directly with GB1 C-terminal via its hypothetical inter-protein
β-sheet structure.
Key Words : Rap1, GABA, GABAB receptor, protein-protein interaction