spacer gif spacer gif spacer gif spacer gif Propose a workshop for 2011 spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search    

The fully linked HTML version of this article has now been published.
JCS ePress online publication date 19 Jul 2005
doi: 10.1242/jcs.02481

This Article
Right arrow Full Text (PDF)
Right arrowOA All Versions of this Article:
jcs.02481v1
118/15/3523    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Peng, X. M.
Right arrow Articles by Perez, R. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Peng, X. M.
Right arrow Articles by Perez, R. G.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Research Article

{alpha}-Synuclein activation of protein phosphatase 2A reduces tyrosine hydroxylase phosphorylation in dopaminergic cells


Xiangmin M. Peng, Roya Tehranian, Paula Dietrich, Leonidas Stefanis, and Ruth G. Perez*
* Author for correspondence (e-mail: perezrg{at}pitt.edu)

{alpha}-Synuclein is an abundant presynaptic protein implicated in neuronal plasticity and neurodegenerative diseases. Although the function of {alpha}-synuclein is not thoroughly elucidated, we found that {alpha}-synuclein regulates dopamine synthesis by binding to and inhibiting tyrosine hydroxylase, the rate limiting enzyme in dopamine synthesis. Understanding {alpha}-synuclein function in dopaminergic cells should add to our knowledge of this key protein, which is implicated in Parkinson's disease and other disorders. Herein, we report a mechanism by which {alpha}-synuclein diminishes tyrosine hydroxylase phosphorylation and activity in stably transfected dopaminergic cells. Short-term regulation of tyrosine hydroxylase depends on the phosphorylation of key seryl residues in the amino-terminal regulatory domain of the protein. Of these, Ser40 contributes significantly to tyrosine hydroxylase activation and dopamine synthesis. We observed that {alpha}-synuclein overexpression caused reduced Ser40 phosphorylation in MN9D cells and inducible PC12 cells. Ser40 is phosphorylated chiefly by the cyclic AMP-dependent protein kinase PKA and dephosphorylated almost exclusively by the protein phosphatase, PP2A. Therefore, we measured the impact of {alpha}-synuclein overexpression on levels and activity of PKA and PP2A in our cells. PKA was unaffected by {alpha}-synuclein. PP2A protein levels also were unchanged, however, the activity of PP2A increased in parallel with {alpha}-synuclein expression. Inhibition of PP2A dramatically increased Ser40 phosphorylation only in {alpha}-synuclein overexpressors in which {alpha}-synuclein was also found to co-immunoprecipitate with PP2A. Together the data reveal a functional interaction between {alpha}-synuclein and PP2A that leads to PP2A activation and underscores a key role for {alpha}-synuclein in protein phosphorylation.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:


Home page
 Mol. Biol. CellHome page
V. L. Sousa, S. Bellani, M. Giannandrea, M. Yousuf, F. Valtorta, J. Meldolesi, and E. Chieregatti
{alpha}-Synuclein and Its A30P Mutant Affect Actin Cytoskeletal Structure and Dynamics
Mol. Biol. Cell, August 15, 2009; 20(16): 3725 - 3739.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. Wang, H. Lou, C. J. Pedersen, A. D. Smith, and R. G. Perez
14-3-3{zeta} Contributes to Tyrosine Hydroxylase Activity in MN9D Cells: LOCALIZATION OF DOPAMINE REGULATORY PROTEINS TO MITOCHONDRIA
J. Biol. Chem., May 22, 2009; 284(21): 14011 - 14019.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
O. S. Gorbatyuk, S. Li, L. F. Sullivan, W. Chen, G. Kondrikova, F. P. Manfredsson, R. J. Mandel, and N. Muzyczka
The phosphorylation state of Ser-129 in human {alpha}-synuclein determines neurodegeneration in a rat model of Parkinson disease
PNAS, January 15, 2008; 105(2): 763 - 768.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
C. Y. Chung, J. B. Koprich, S. Endo, and O. Isacson
An Endogenous Serine/Threonine Protein Phosphatase Inhibitor, G-Substrate, Reduces Vulnerability in Models of Parkinson's Disease
J. Neurosci., August 1, 2007; 27(31): 8314 - 8323.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
D. Zhang, A. Kanthasamy, Y. Yang, V. Anantharam, and A. Kanthasamy
Protein Kinase C{delta} Negatively Regulates Tyrosine Hydroxylase Activity and Dopamine Synthesis by Enhancing Protein Phosphatase-2A Activity in Dopaminergic Neurons
J. Neurosci., May 16, 2007; 27(20): 5349 - 5362.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
K. E. Larsen, Y. Schmitz, M. D. Troyer, E. Mosharov, P. Dietrich, A. Z. Quazi, M. Savalle, V. Nemani, F. A. Chaudhry, R. H. Edwards, et al.
{alpha}-Synuclein Overexpression in PC12 and Chromaffin Cells Impairs Catecholamine Release by Interfering with a Late Step in Exocytosis.
J. Neurosci., November 15, 2006; 26(46): 11915 - 11922.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
S. A. Austin, A. M. Floden, E. J. Murphy, and C. K. Combs
{alpha}-Synuclein Expression Modulates Microglial Activation Phenotype
J. Neurosci., October 11, 2006; 26(41): 10558 - 10563.
[Abstract] [Full Text] [PDF]


© The Company of Biologists Ltd 2005