Heart-Type Fatty Acid Binding Protein Regulates Dopamine D<sub>2</sub>Receptor Function in Mouse Brain

Shioda, Norifumi; Yamamoto, Yoshiyuki; Watanabe, Masahiko; Binas, Bert; Owada, Yuji; Fukunaga, Kohji

doi:10.1523/jneurosci.4140-09.2010

Cited by 88 publications

(79 citation statements)

References 67 publications

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“…Taken together, these observations allow the speculation that FABP3 could play a role in testosterone production by transporting the required AA from other cellular sites to mitochondria. Although there are studies using Fabp3 knockdown mice to define FABP3 functions in different tissues (Schachtrup et al 2008, Shioda et al 2010, no one has yet informed of the effects of such gene change on testicular function.…”

Section: Discussionmentioning

confidence: 99%

Cell-type-specific regulation of genes involved in testicular lipid metabolism: fatty acid-binding proteins, diacylglycerol acyltransferases, and perilipin 2

Oresti¹,

García-López²,

Aveldaño³

et al. 2013

Reproduction

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Male germ cell differentiation entails the synthesis and remodeling of membrane polar lipids and the formation of triacylglycerols (TAGs). This requires fatty acid-binding proteins (FABPs) for intracellular fatty acid traffic, a diacylglycerol acyltransferase (DGAT) to catalyze the final step of TAG biosynthesis, and a TAG storage mode. We examined the expression of genes encoding five members of the FABP family and two DGAT proteins, as well as the lipid droplet protein perilipin 2 (PLIN2), during mouse testis development and in specific cells from seminiferous epithelium. Fabp5 expression was distinctive of Sertoli cells and consequently was higher in prepubertal than in adult testis. The expression of Fabp3 increased in testis during postnatal development, associated with the functional differentiation of interstitial cells, but was low in germ cells. Fabp9, together with Fabp12, was prominently expressed in the latter. Their transcripts increased from spermatocytes to spermatids and, interestingly, were highest in spermatid-derived residual bodies (RB). Both Sertoli and germ cells, which produce neutral lipids and store them in lipid droplets, expressed Plin2. Yet, while Dgat1 was detected in Sertoli cells, Dgat2 accumulated in germ cells with a similar pattern of expression as Fabp9. These results correlated with polyunsaturated fatty acid-rich TAG levels also increasing with mouse germ cell differentiation highest in RB, connecting DGAT2 with the biosynthesis of such TAGs. The age-and germ cell type-associated increases in Fabp9, Dgat2, and Plin2 levels are thus functionally related in the last stages of germ cell differentiation.

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Section: Discussionmentioning

confidence: 99%

Cell-type-specific regulation of genes involved in testicular lipid metabolism: fatty acid-binding proteins, diacylglycerol acyltransferases, and perilipin 2

Oresti¹,

García-López²,

Aveldaño³

et al. 2013

Reproduction

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“…Immunohistochemical studies were performed as previously described (Shioda et al, 2010a). Briefly, 50-mthick brain sections were incubated for 30 min in PBS containing 0.01% Triton X-100, in blocking solution for 1 h, and with various primary antibodies in blocking solution at 20°C for 5 d. Antibodies included mouse monoclonal antibodies against microtubule-associated protein-2 (MAP-2) (1:1000, Millipore); neuronal nuclear antigen (NeuN) (1:1000, Millipore); glial fibrillary acidic protein (GFAP) (1:1000, Sigma-Aldrich); and rabbit polyclonal antibody against ATRX (H-300, 1:1000, Santa Cruz Biotechnology).…”

Section: Animals Generation Of Homozygous Atrxmentioning

confidence: 99%

“…Immunoprecipitation and immunoblotting analysis was performed as previously described (Shioda et al, 2010a). Mouse brains were immediately removed and perfused in ice-cold buffer for 3 min (0.32 M sucrose, 20 mM TrisHCl, pH 7.4).…”

Section: Animals Generation Of Homozygous Atrxmentioning

confidence: 99%

Aberrant Calcium/Calmodulin-Dependent Protein Kinase II (CaMKII) Activity Is Associated with Abnormal Dendritic Spine Morphology in theATRXMutant Mouse Brain

Shioda¹,

Beppu²,

Fukuda³

et al. 2011

J. Neurosci.

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In humans, mutations in the gene encoding ATRX, a chromatin remodeling protein of the sucrose-nonfermenting 2 family, cause several mental retardation disorders, including ␣-thalassemia X-linked mental retardation syndrome. We generated ATRX mutant mice lacking exon 2 (ATRX ⌬E2 mice), a mutation that mimics exon 2 mutations seen in human patients and associated with milder forms of retardation. ATRX ⌬E2 mice exhibited abnormal dendritic spine formation in the medial prefrontal cortex (mPFC). Consistent with other mouse models of mental retardation, ATRX ⌬E2 mice exhibited longer and thinner dendritic spines compared with wild-type mice without changes in spine number. Interestingly, aberrant increased calcium/calmodulin-dependent protein kinase II (CaMKII) activity was observed in the mPFC of ATRX ⌬E2 mice. Increased CaMKII autophosphorylation and activity were associated with increased phosphorylation of the Rac1-guanine nucleotide exchange factors (GEFs) T-cell lymphoma invasion and metastasis 1 (Tiam1) and kalirin-7, known substrates of CaMKII. We confirmed increased phosphorylation of p21-activated kinases (PAKs) in mPFC extracts. Furthermore, reduced protein expression and activity of protein phosphatase 1 (PP1) was evident in the mPFC of ATRX ⌬E2 mice. In cultured cortical neurons, PP1 inhibition by okadaic acid increased CaMKII-dependent Tiam1 and kalirin-7 phosphorylation. Together, our data strongly suggest that aberrant CaMKII activation likely mediates abnormal spine formation in the mPFC. Such morphological changes plus elevated Rac1-GEF/PAK signaling seen in ATRX ⌬E2 mice may contribute to mental retardation syndromes seen in human patients.

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“…Brain-type (B-) FABP did not bind to D2LR-YFP (27). Likewise, the immunocomplex with anti-D2LR antibody using the striatal cell extracts included H-FABP in wild-type mice, but not in H-FABP knockout (KO) mice (28).…”

Section: H-fabp Is a Novel Protein That Interacts With A Unique Residmentioning

confidence: 99%

“…H-FABP protein is also expressed in glutamatergic terminals in the dorsal striatum, whereas H-FABP is not present in dopaminergic terminals or in postsynaptic densities in dendritic spines of mediumsized spiny neurons in the dorsal striatum. In H-FABPexpressing regions, D2R was also present in cell bodies of cholinergic neurons and in glutamatergic terminals in the dorsal striatum (28). Interestingly, H-FABP KO mice exhibit D2R dysfunction, based on evaluation of dopamine-related behaviors (28).…”

Section: H-fabp Is a Novel Protein That Interacts With A Unique Residmentioning

confidence: 99%

Advanced Research on Dopamine Signaling to Develop Drugs for the Treatment of Mental Disorders: Proteins Interacting With the Third Cytoplasmic Loop of Dopamine D2 and D3 Receptors

Shioda¹,

Takeuchi²,

Fukunaga³

2010

J Pharmacol Sci

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Abstract. Among the various dopamine receptors, D 2 -like receptors (D2R, D3R, and D4R) are characterized by a large third cytoplasmic loop, a short carboxyl-terminal tail, and the ability to activate inhibitory G proteins. The diverse activities of D 2 -like receptors are partly mediated by proteins that interact with the third cytoplasmic loop, which regulate receptor signaling, receptor trafficking, and stability. Furthermore, in the case of D2R and D3R genes, mRNA splicing generates isoforms in the region of the third cytoplasmic loop. The gene encoding D2R gives rise to two isoforms, termed the dopamine D 2 receptor long isoform (D2LR) and the dopamine D 2 receptor short isoform (D2SR), which lacks 29 amino acids of the D2LR within the third cytoplasmic loop. The D3R gene also produces at least seven distinct alternative splicing variants including D3nf, in which 98 base pairs in the carboxyl-terminal region of the third intracellular loop are deleted. In this review, we focus on proteins interacting with the dopamine D 2 /D 3 receptors in the third cytoplasmic loop. We also define a novel binding protein, heart-type fatty acid-binding protein (H-FABP), which specifically interacts with the 29 D2LR amino acids deleted in D2SR and document its function in D2LR signaling.

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Heart-Type Fatty Acid Binding Protein Regulates Dopamine D₂Receptor Function in Mouse Brain

Cited by 88 publications

References 67 publications

Cell-type-specific regulation of genes involved in testicular lipid metabolism: fatty acid-binding proteins, diacylglycerol acyltransferases, and perilipin 2

Cell-type-specific regulation of genes involved in testicular lipid metabolism: fatty acid-binding proteins, diacylglycerol acyltransferases, and perilipin 2

Aberrant Calcium/Calmodulin-Dependent Protein Kinase II (CaMKII) Activity Is Associated with Abnormal Dendritic Spine Morphology in theATRXMutant Mouse Brain

Advanced Research on Dopamine Signaling to Develop Drugs for the Treatment of Mental Disorders: Proteins Interacting With the Third Cytoplasmic Loop of Dopamine D2 and D3 Receptors

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Heart-Type Fatty Acid Binding Protein Regulates Dopamine D2Receptor Function in Mouse Brain

Cited by 88 publications

References 67 publications

Cell-type-specific regulation of genes involved in testicular lipid metabolism: fatty acid-binding proteins, diacylglycerol acyltransferases, and perilipin 2

Cell-type-specific regulation of genes involved in testicular lipid metabolism: fatty acid-binding proteins, diacylglycerol acyltransferases, and perilipin 2

Aberrant Calcium/Calmodulin-Dependent Protein Kinase II (CaMKII) Activity Is Associated with Abnormal Dendritic Spine Morphology in theATRXMutant Mouse Brain

Advanced Research on Dopamine Signaling to Develop Drugs for the Treatment of Mental Disorders: Proteins Interacting With the Third Cytoplasmic Loop of Dopamine D2 and D3 Receptors

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Heart-Type Fatty Acid Binding Protein Regulates Dopamine D₂Receptor Function in Mouse Brain