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The Journal of Neuroscience, January 17, 2007, 27(3):449-458; doi:10.1523/JNEUROSCI.4489-06.2007

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Cellular/Molecular
The Cationic Amino Acid Transporters CAT1 and CAT3 Mediate NMDA Receptor Activation-Dependent Changes in Elaboration of Neuronal Processes via the Mammalian Target of Rapamycin mTOR Pathway

Yunfei Huang,¹ Bingnan N. Kang,^1,2 Jing Tian,¹ Yi Liu,¹ Hongbo R. Luo,⁴ Lynda Hester,¹ and Solomon H. Snyder^1,2,3

¹The Solomon H. Snyder Department of Neuroscience and Departments of ²Pharmacology and Molecular Sciences and ³Psychiatry and Behavioral Sciences, Johns Hopkins University, School of Medicine, Baltimore, Maryland 21205, and ⁴Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115

Correspondence should be addressed to Solomon H. Snyder, Department of Neuroscience, Johns Hopkins University, School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205. Email: ssnyder{at}bs.jhmi.edu

Neuronal activity influences protein synthesis and neuronal growth. Availability of nutrients, especially leucine and arginine, regulates the mammalian target of rapamycin (mTOR) pathway that controls cell growth. We show that NMDA receptor activation markedly reduces arginine transport by decreasing surface expression of the cationic amino acid transporters (CAT) 1 and 3. Depletion of CAT1 and CAT3 by RNA interference blocks influences of NMDA receptor activation on the mTOR pathway and neuronal process formation. Thus, the CATs mediate influences of NMDA receptor activation on the mTOR pathway that regulates neuronal processes.

Key words: cationic amino acid transporters; NMDA receptor; mTOR; neurite growth; neuronal activity; uptake

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Received June 9, 2006; revised Dec. 1, 2006; accepted Dec. 3, 2006.

Correspondence should be addressed to Solomon H. Snyder, Department of Neuroscience, Johns Hopkins University, School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205. Email: ssnyder{at}bs.jhmi.edu

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