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

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, April 13, 2005, 25(15):3741-3751; doi:10.1523/JNEUROSCI.0152-05.2005

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 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 Web of Science (21) Citing Articles via Google Scholar Google Scholar Articles by Muresan, Z. Articles by Muresan, V. Search for Related Content PubMed PubMed Citation Articles by Muresan, Z. Articles by Muresan, V.

 Previous Article  |  Next Article 

Cellular/Molecular
c-Jun NH₂-Terminal Kinase-Interacting Protein-3 Facilitates Phosphorylation and Controls Localization of Amyloid- Precursor Protein

Zoia Muresan and Virgil Muresan

Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106-4970

Abnormal phosphorylation of amyloid- precursor protein (APP) is a pathologic feature of Alzheimer's disease. To begin to understand the mechanism of APP phosphorylation, we studied this process in differentiating neurons under normal physiological conditions. We found that c-Jun NH₂-terminal kinase (JNK), not cyclin-dependent kinase 5, is required for APP phosphorylation, leading to localized accumulation of phosphorylated APP (pAPP) in neurites. We show that JNK-interacting protein-3 (JIP-3), a JNK scaffolding protein that does not bind APP, selectively increases APP phosphorylation, accumulation of pAPP into processes, and stimulates process extension in both neurons and COS-1 cells. Downregulation of JIP-3 by small interfering RNA impairs neurite extension and reduces the amount of localized pAPP. Finally, whereas stress-activated JNK generates pAPP only in the cell body, concomitant expression of JIP-3 restores pAPP accumulation into neurites. Thus, APP phosphorylation, transport of the generated pAPP into neurites, and neurite extension are interdependent processes regulated by JIP-3/JNK, in a pathway distinct from stress-activated JNK signaling.

Key words: amyloid- precursor protein; c-Jun NH₂-terminal kinase; JNK-interacting protein; Alzheimer's disease; kinesin; axonal transport

---

Received Jan 12, 2005; revised March 2, 2005; accepted March 4, 2005.

This article has been cited by other articles:

				Z. Wang, B. Wang, L. Yang, Q. Guo, N. Aithmitti, Z. Songyang, and H. Zheng Presynaptic and Postsynaptic Interaction of the Amyloid Precursor Protein Promotes Peripheral and Central Synaptogenesis J. Neurosci., September 2, 2009; 29(35): 10788 - 10801. [Abstract] [Full Text] [PDF]

				V. Muresan, N. H. Varvel, B. T. Lamb, and Z. Muresan The Cleavage Products of Amyloid-{beta} Precursor Protein Are Sorted to Distinct Carrier Vesicles That Are Independently Transported within Neurites J. Neurosci., March 18, 2009; 29(11): 3565 - 3578. [Abstract] [Full Text] [PDF]

				T. Suzuki and T. Nakaya Regulation of Amyloid {beta}-Protein Precursor by Phosphorylation and Protein Interactions J. Biol. Chem., October 31, 2008; 283(44): 29633 - 29637. [Abstract] [Full Text] [PDF]

				Z. Muresan and V. Muresan The Amyloid-beta Precursor Protein Is Phosphorylated via Distinct Pathways during Differentiation, Mitosis, Stress, and Degeneration Mol. Biol. Cell, October 1, 2007; 18(10): 3835 - 3844. [Abstract] [Full Text] [PDF]

				M. Stagi, P. Gorlovoy, S. Larionov, K. Takahashi, and H. Neumann Unloading kinesin transported cargoes from the tubulin track via the inflammatory c-Jun N-terminal kinase pathway FASEB J, December 1, 2006; 20(14): 2573 - 2575. [Abstract] [Full Text] [PDF]

				P. Satpute-Krishnan, J. A. DeGiorgis, M. P. Conley, M. Jang, and E. L. Bearer A peptide zipcode sufficient for anterograde transport within amyloid precursor protein PNAS, October 31, 2006; 103(44): 16532 - 16537. [Abstract] [Full Text] [PDF]

				Z. Muresan and V. Muresan Neuritic Deposits of Amyloid-{beta} Peptide in a Subpopulation of Central Nervous System-Derived Neuronal Cells. Mol. Cell. Biol., July 1, 2006; 26(13): 4982 - 4997. [Abstract] [Full Text] [PDF]

				Z. Muresan and V. Muresan Coordinated transport of phosphorylated amyloid-{beta} precursor protein and c-Jun NH2-terminal kinase-interacting protein-1 J. Cell Biol., November 21, 2005; 171(4): 615 - 625. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help