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The Journal of Neuroscience, March 1, 2003, 23(5):1667

Interaction between Liprin- and GIT1 Is Required for AMPA Receptor Targeting

Jaewon Ko¹, Seho Kim¹, Juli G. Valtschanoff², Hyewon Shin¹, Jae-Ran Lee¹, Morgan Sheng³, Richard T. Premont⁴, Richard J. Weinberg², and Eunjoon Kim¹

¹ Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea, ² Department of Cell Biology and Anatomy, University of North Carolina Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, ³ Center for Learning and Memory, RIKEN-MIT Neuroscience Research Center and Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, and ⁴ Department of Medicine (Gastroenterology), Duke University Medical Center, Durham, North Carolina 27710

Liprin- is a multidomain protein that interacts with the LAR family of receptor protein tyrosine phosphatases and the GRIP/ABP family of AMPA receptor-interacting proteins. Previous studies have indicated that liprin- regulates the development of presynaptic active zones and that the association of liprin- with GRIP is required for postsynaptic targeting of AMPA receptors. However, the underlying molecular mechanisms are not well understood. Here we report that liprin- directly interacts with GIT1, a multidomain protein with GTPase-activating protein activity for the ADP-ribosylation factor family of small GTPases known to regulate protein trafficking and the actin cytoskeleton. Electron microscopic analysis indicates that GIT1 distributes to the region of postsynaptic density (PSD) as well as presynaptic active zones. GIT1 is enriched in PSD fractions and forms a complex with liprin-, GRIP, and AMPA receptors in brain. Expression of dominant-negative constructs interfering with the GIT1-liprin- interaction leads to a selective and marked reduction in the dendritic and surface clustering of AMPA receptors in cultured neurons. These results suggest that the GIT1-liprin- interaction is required for AMPA receptor targeting and that GIT1 may play an important role in the organization of presynaptic and postsynaptic multiprotein complexes.

Key words: postsynaptic density; GIT1; liprin; GRIP; ABP; AMPA receptor

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Copyright © 2003 Society for Neuroscience  0270-6474/03/2351667-11$05.00/0

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