14-3-3ζ Contributes to Tyrosine Hydroxylase Activity in MN9D Cells

Wang, Jian; Lou, Haiyan; Pedersen, Courtney J.; Smith, Amanda D.; Perez, Ruth G.

doi:10.1074/jbc.m901310200

Cited by 71 publications

(42 citation statements)

References 60 publications

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“…This last point is especially relevant, considering that TH exists as two subcellular forms, cytosolic and membrane-bound (19 -22). Recently, active TH has also been demonstrated to associate with mitochondria, further supporting the notion of multiple cytosolic and membrane-bound TH pools (35). Further studies will therefore be required to determine what portion of total TH interacts with VMAT 2 and is membrane-bound as well as to understand the molecular determinants that modulate this association.…”

Section: Discussionmentioning

confidence: 99%

A Biochemical and Functional Protein Complex Involving Dopamine Synthesis and Transport into Synaptic Vesicles

Cartier

Parra

Baust

et al. 2010

Journal of Biological Chemistry

115

103

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Synaptic transmission depends on neurotransmitter pools stored within vesicles that undergo regulated exocytosis. In the brain, the vesicular monoamine transporter-2 (VMAT 2 ) is responsible for the loading of dopamine (DA) and other monoamines into synaptic vesicles. Prior to storage within vesicles, DA synthesis occurs at the synaptic terminal in a two-step enzymatic process. First, the rate-limiting enzyme tyrosine hydroxylase (TH) converts tyrosine to di-OH-phenylalanine. Aromatic amino acid decarboxylase (AADC) then converts di-OH-phenylalanine into DA. Here, we provide evidence that VMAT 2 physically and functionally interacts with the enzymes responsible for DA synthesis. In rat striata, TH and AADC co-immunoprecipitate with VMAT 2 , whereas in PC 12 cells, TH co-immunoprecipitates with the closely related VMAT 1 and with overexpressed VMAT 2 . GST pull-down assays further identified three cytosolic domains of VMAT 2 involved in the interaction with TH and AADC. Furthermore, in vitro binding assays demonstrated that TH directly interacts with VMAT 2 . Additionally, using fractionation and immunoisolation approaches, we demonstrate that TH and AADC associate with VMAT 2 -containing synaptic vesicles from rat brain. These vesicles exhibited specific TH activity. Finally, the coupling between synthesis and transport of DA into vesicles was impaired in the presence of fragments involved in the VMAT 2 /TH/AADC interaction. Taken together, our results indicate that DA synthesis can occur at the synaptic vesicle membrane, where it is physically and functionally coupled to VMAT 2 -mediated transport into vesicles.Monoamines, including dopamine (DA), 3 norepinephrine (NE), and serotonin (5-HT), are neurotransmitters that play major roles in a variety of brain functions, including emotion, reward, cognition, memory, attention, locomotion, and stress control (1-6). In neurons and neuroendocrine cells, monoamines are stored in large dense core vesicles (LDCVs) and small synaptic vesicles (SVs) (7-11) that undergo regulated exocytosis through a complex network of protein-protein interactions (12). Loading of monoamines into LDCVs and SVs of neurons and neuroendocrine cells is mediated by two vesicular monoamine transporter isoforms: VMAT 1 (13) and VMAT 2 (14). These transporters contain 12 putative transmembrane domains with both the N and C termini facing the cytosolic side of the vesicle membrane. VMAT 1 is mostly present in LDCVs of neuroendocrine cells, including chromaffin and PC12 cells, whereas VMAT 2 is primarily expressed by monoaminergic neurons of the central nervous system (15). In midbrain DA neurons, VMAT 2 is sorted to LDCVs and SVs in axon terminals and to LDCVs and tubulo-vesicular structures in the somatodendritic compartment (7)(8)(9)(10)(11)15).It is generally accepted that VMAT 2 transports DA that has been previously synthesized in the cytosolic compartment of the presynaptic terminal (16). DA synthesis requires two enzymatic reactions. First, tyrosine hydroxylase (TH) converts tyrosine into DOP...

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Section: Discussionmentioning

confidence: 99%

A Biochemical and Functional Protein Complex Involving Dopamine Synthesis and Transport into Synaptic Vesicles

Cartier

Parra

Baust

et al. 2010

Journal of Biological Chemistry

115

103

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“…DJ-1 therefore stimulates TH activity both by up-regulation of TH gene expression and by protein-protein interaction, and DJ-1 stimulates DDC activity only by protein-protein interaction. Phosphorylation of Ser-19 of TH by various kinases stimulates TH activity (25)(26)(27)(28). Introduction of DJ-1 in vitro and in vivo, however, did not stimulate phosphorylation of TH, although its activity was increased ( Fig.…”

Section: Discussionmentioning

confidence: 99%

Oxidative Status of DJ-1-dependent Activation of Dopamine Synthesis through Interaction of Tyrosine Hydroxylase and 4-Dihydroxy-l-phenylalanine (l-DOPA) Decarboxylase with DJ-1

Ishikawa

Taira

Niki

et al. 2009

Journal of Biological Chemistry

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Parkinson disease (PD) is caused by loss of dopamine, which is synthesized from tyrosine by two enzymes, tyrosine hydroxylase (TH) and 4-dihydroxy-L-phenylalanine decarboxylase (DDC).DJ-1 is a causative gene for the familial form of PD, but little is known about the roles of DJ-1 in dopamine synthesis. In this study, we found that DJ-1 directly bound to TH and DDC and positively regulated their activities in human dopaminergic cells. Mutants of DJ-1 found in PD patients, including heterozygous mutants, lost their activity and worked as dominant-negative forms toward wild-type DJ-1. When cells were treated with H 2 O 2 , 6-hydroxydopamine, or 1-methyl-4-phenylpyridinium, changes in activities of TH and DDC accompanied by oxidation of cysteine 106 of DJ-1 occurred. It was found that DJ-1 possessing Cys-106 with SH and SOH forms was active and that DJ-1 possessing Cys-106 with SO 2 H and SO 3 H forms was inactive in terms of stimulation of TH and DDC activities. These findings indicate an essential role of DJ-1 in dopamine synthesis and contribution of DJ-1 to the sporadic form of PD. Parkinson disease (PD)2 is a neurodegenerative disease that occurs by reduction of the dopamine level through dopaminergic cell death in the substantia nigra. Genetic and environmental factors are thought to be triggers for the onset of PD, but the precise molecular mechanisms are still not known. Dopamine is synthesized by the following two steps: tyrosine is converted to L-DOPA by tyrosine hydroxylase (TH) and then L-DOPA is converted to dopamine by L-dopa decarboxylase (DDC). TH is therefore a key enzyme for dopamine synthesis and is used as a marker for dopaminergic neurons.DJ-1 was first identified by our group as a novel candidate of the oncogene that transformed mouse NIH3T3 cells in cooperation with activated ras (1). Deletion and point (L166P) mutations of DJ-1 have been shown to be responsible for onset of familial Parkinson disease, PARK7 (2), and other homozygous and heterozygous mutations of DJ-1 have been identified in patients with familial or sporadic Parkinson disease (3-6). DJ-1 is a multifunctional protein and plays roles in transcriptional regulation and anti-oxidative stress function, and loss of its functions is thought to lead to the onset of Parkinson disease and cancer. DJ-1 has three cysteine residues at positions 46, 53, and 106 (Cys-46, Cys-53, and Cys-106, respectively), and these cysteine residues are oxidized after cells receive oxidative stress, resulting in scavenging of reactive oxidative species (7-12). Although DJ-1 does not directly bind to DNA, DI-1 acts as a co-activator to activate various transcription factors, including the androgen receptor and p53 tumor suppressor, PSF and Nrf2, by sequestering their inhibitory factors (13-18). The anti-oxidative stress function of DJ-1 is therefore thought to be carried out both by self-oxidation of cysteine residues and by activation of redox-related genes.It has been reported that PSF, a transcription repressor, binds to the promoter region of the TH gene...

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“…Interestingly, the biosynthetic enzymes involved in catecholamine degradation, the monoamine oxidases MAO-A and MAO-B are anchored to the outer mitochondrial membrane (Binda et al, 2011). Some reports also suggest that TH may be tethered to the mitochondrial surface (Wang et al, 2009; Baumann et al, 2016), although this may be tissue specific and inducible under certain conditions; more work is needed to examine this potential functional association of mitochondria with catecholamine synthesis and degradation.…”

Section: Mitochondria Synthesize and Metabolize Glucocorticoids Anmentioning

confidence: 99%

An energetic view of stress: Focus on mitochondria

Picard

McEwen

Epel

et al. 2018

Frontiers in Neuroendocrinology

402

309

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Energy is required to sustain life and enable stress adaptation. At the cellular level, energy is largely derived from mitochondria – unique multifunctional organelles with their own genome. Four main elements connect mitochondria to stress: (1) Energy is required at the molecular, (epi)genetic, cellular, organellar, and systemic levels to sustain components of stress responses; (2) Glucocorticoids and other steroid hormones are produced and metabolized by mitochondria; (3) Reciprocally, mitochondria respond to neuroendocrine and metabolic stress mediators; and (4) Experimentally manipulating mitochondrial functions alters physiological and behavioral responses to psychological stress. Thus, mitochondria are endocrine organelles that provide both the energy and signals that enable and direct stress adaptation. Neural circuits regulating social behavior – as well as psychopathological processes – are also influenced by mitochondrial energetics. An integrative view of stress as an energy-driven process opens new opportunities to study mechanisms of adaptation and regulation across the lifespan.

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14-3-3ζ Contributes to Tyrosine Hydroxylase Activity in MN9D Cells

Cited by 71 publications

References 60 publications

A Biochemical and Functional Protein Complex Involving Dopamine Synthesis and Transport into Synaptic Vesicles

A Biochemical and Functional Protein Complex Involving Dopamine Synthesis and Transport into Synaptic Vesicles

Oxidative Status of DJ-1-dependent Activation of Dopamine Synthesis through Interaction of Tyrosine Hydroxylase and 4-Dihydroxy-l-phenylalanine (l-DOPA) Decarboxylase with DJ-1

An energetic view of stress: Focus on mitochondria

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