The Journal of Neuroscience, February 1, 2003, 23(3):748
The RAS Effector RIN1 Modulates the Formation of Aversive
Memories
Ajay
Dhaka,
Rui M.
Costa2,
Hailiang
Hu1,
Dwain K.
Irvin3,
Apoor
Patel1,
Harley I.
Kornblum3,
Alcino J.
Silva2,
Thomas J.
O'Dell4, and
John
Colicelli1
Departments of 1 Biological Chemistry,
2 Neurobiology, 3 Molecular and Medical
Pharmacology, and 4 Physiology, and Molecular Biology
Institute, University of California, Los Angeles School of Medicine,
Los Angeles, California 90095-1737
RAS proteins are critical regulators of mitosis and are
mutationally activated in many human tumors. RAS signaling is also known to mediate long-term potentiation (LTP) and long-term memory formation in postmitotic neurons, in part through activation of the
RAF-MEK-ERK pathway. The RAS effector RIN1 appears to function through competitive inhibition of RAS-RAF binding and also through diversion of RAS signaling to alternate pathways. We show that RIN1 is
preferentially expressed in postnatal forebrain neurons in which it is
localized in dendrites and physically associated with RAS, suggesting a
role in RAS-mediated postsynaptic neuronal plasticity. Mice with an
Rin1 gene disruption showed a striking enhancement in
amygdala LTP. In addition, two independent behavioral tests
demonstrated elevated amygdala-dependent aversive memory in
Rin1
/ mice. These results indicate
that RIN1 serves as an inhibitory modulator of neuronal plasticity in
aversive memory formation.
Key words:
RIN1; RAS; ABL; amygdala; aversive memory; hippocampus; LTP; dendrites
Copyright © 2003 Society for Neuroscience 0270-6474/03/233748-10$05.00/0
Previous Article | Next Article
