QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, March 1, 2006, 26(9):2380-2390; doi:10.1523/JNEUROSCI.3503-05.2006

This Article Full Text Full Text (PDF) Supplemental data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (15) Citing Articles via Google Scholar Google Scholar Articles by Jin, W. Articles by Xia, J. Search for Related Content PubMed PubMed Citation Articles by Jin, W. Articles by Xia, J.

 Previous Article  |  Next Article 

Cellular/Molecular
Lipid Binding Regulates Synaptic Targeting of PICK1, AMPA Receptor Trafficking, and Synaptic Plasticity

Wenying Jin,¹ Woo-Ping Ge,² Junyu Xu,¹ Mian Cao,¹ Lisheng Peng,¹ Wingho Yung,³ Dezhi Liao,⁴ Shumin Duan,² Mingjie Zhang,¹ and Jun Xia¹

¹Department of Biochemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China, ²Institute of Neuroscience, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China, ³Department of Physiology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China, and ⁴Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota 55455

Correspondence should be addressed to Dr. Jun Xia, Department of Biochemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China. Email: jxia{at}ust.hk

The targeting and surface expression of membrane proteins are critical to their functions. In neurons, synaptic targeting and surface expression of AMPA-type glutamate receptors were found to be critical for synaptic plasticity such as long-term potentiation and long-term depression (LTD). PICK1 (protein interacting with C kinase 1) is a cytosolic protein that interacts with many membrane proteins, including AMPA receptors via its PDZ (postsynaptic density-95/Discs large/zona occludens-1) domain. Its interactions with membrane proteins regulate their subcellular targeting and surface expression. However, the mechanism by which PICK1 regulates protein trafficking has not been fully elucidated. Here, we show that PICK1 directly binds to lipids, mainly phosphoinositides, via its BAR (Bin/amphiphysin/Rvs) domain. Lipid binding of the PICK1 BAR domain is positively regulated by its PDZ domain and negatively regulated by its C-terminal acidic domain. Mutation of critical residues of the PICK1 BAR domain eliminates its lipid-binding capability. Lipid binding of PICK1 controls the subcellular localization of the protein, because BAR domain mutant of PICK1 has diminished synaptic targeting compared with wild-type PICK1. In addition, the BAR domain mutant of PICK1 does not cluster AMPA receptors. Moreover, wild-type PICK1 enhances synaptic targeting of AMPA receptors, whereas the BAR domain mutant of PICK1 fails to do so. The BAR domain mutant of PICK1 loses its ability to regulate surface expression of the AMPA receptors and impairs expression of LTD in hippocampal neurons. Together, our findings indicate that the lipid binding of the PICK1 BAR domain is important for its synaptic targeting, AMPA receptor trafficking, and synaptic plasticity.

Key words: PICK1; AMPA receptor; synaptic plasticity; LTD; PDZ domain; BAR domain

---

Received June 12, 2005; revised Jan. 10, 2006; accepted Jan. 11, 2006.

Correspondence should be addressed to Dr. Jun Xia, Department of Biochemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China. Email: jxia{at}ust.hk

This article has been cited by other articles:

				M. Cao, J. Xu, C. Shen, C. Kam, R. L. Huganir, and J. Xia PICK1 ICA69 Heteromeric BAR Domain Complex Regulates Synaptic Targeting and Surface Expression of AMPA Receptors J. Neurosci., November 21, 2007; 27(47): 12945 - 12956. [Abstract] [Full Text] [PDF]

				M. T.-W. Ho, K. A. Pelkey, L. Topolnik, R. S. Petralia, K. Takamiya, J. Xia, R. L. Huganir, J.-C. Lacaille, and C. J. McBain Developmental Expression of Ca2+-Permeable AMPA Receptors Underlies Depolarization-Induced Long-Term Depression at Mossy Fiber CA3 Pyramid Synapses J. Neurosci., October 24, 2007; 27(43): 11651 - 11662. [Abstract] [Full Text] [PDF]

				M. Joch, A. R. Ase, C. X.-Q. Chen, P. A. MacDonald, M. Kontogiannea, A. T. Corera, A. Brice, P. Seguela, and E. A. Fon Parkin-mediated Monoubiquitination of the PDZ Protein PICK1 Regulates the Activity of Acid-sensing Ion Channels Mol. Biol. Cell, August 1, 2007; 18(8): 3105 - 3118. [Abstract] [Full Text] [PDF]

				Z.-W. Chen, C.-S. S. Chang, T. A. Leil, and R. W. Olsen C-Terminal Modification Is Required for GABARAP-Mediated GABAA Receptor Trafficking J. Neurosci., June 20, 2007; 27(25): 6655 - 6663. [Abstract] [Full Text] [PDF]

				E. A. Horne and M. L. Dell'Acqua Phospholipase C Is Required for Changes in Postsynaptic Structure and Function Associated with NMDA Receptor-Dependent Long-Term Depression J. Neurosci., March 28, 2007; 27(13): 3523 - 3534. [Abstract] [Full Text] [PDF]

				P. Arstikaitis and C. Gauthier-Campbell BARS at the Synapse: PICK-1 Lipid Binding Domain Regulates Targeting, Trafficking, and Synaptic Plasticity J. Neurosci., June 28, 2006; 26(26): 6909 - 6910. [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help