Biomedical subjects

Qing Wang

Publications and source records attributed to Qing Wang.

At least 145 records · Page 8Linked to original sources

PubMed2003

D1 ring is stable and nucleotide-independent, whereas D2 ring undergoes major conformational changes during the ATPase cycle of p97-VCP.

The 97-kDa valosin-containing protein (p97-VCP) belongs to the AAA (ATPases associated with various cellular activities) family and acts as a molecular chaperone in diverse cellular events, including ubiquitinproteasome-mediated degradation. We previously showed that VCP contains a substrate-binding domain, N, and two conserved ATPase domains, D1 and D2, of which D2 is responsible for the major enzyme activity. VCP has a barrel-like structure containing two stacked homo-hexameric rings made of the D1 and D2 domains, and this structure is essential for its biological functions. During ATPase cycles, VCP undergoes conformational changes that presumably apply tensions to the bound substrate, leading to the disassembly of protein complexes or unfolding of the substrate. How ATPase activity is coupled with the conformational changes in VCP complex and the D1 and D2 rings is not clear. In this report, we took biochemical approaches to study the structure of VCP in different nucleotide conditions to depict the conformational changes in the ATPase cycles. In contrast to many AAA chaperones that require ATP/ADP to form oligomers, both wild type VCP and ATP-binding site mutants can form hexamers without the addition of nucleotide. This nucleotide-independent hexamerization requires an intact D1 and the down-stream linker sequence of VCP. Tryptophan fluorescence and trypsin digestion analyses showed that ATP/ADP binding induces dramatic conformational changes in VCP. These changes do not require the presence of an intact ATP-binding site in D1 and is thus mainly attributed to the D2 domain. We propose a model whereby D1, although undergoing minor conformational changes, remains as a relatively trypsin-resistant hexameric ring throughout the ATPase cycle, whereas D2 only does so when it binds to ATP or ADP. After ADP is released at the end of the ATP hydrolysis, D2 ring is destabilized and adopts a relatively flexible and open structure.

Adenosine Diphosphate↗

PubMed2003

Cytogenetic analysis of obsessive-compulsive disorder (OCD): identification of a FRAXE fragile site.

Obsessive-compulsive disorder (OCD) is a chronic psychiatric disease characterized by recurrent obsessions, compulsions, or both. The prevalence rate of OCD is 2.1% in the general population. Here we report cytogenetic analysis of 26 patients affected with OCD. In one male patient (OCD-K33), we identified a fragile X chromosome by cytogenetic analysis with 21% of cells demonstrating a fragile site at Xq27-q28. Polymerase chain reaction (PCR) and Southern blot analysis demonstrated that the molecular basis of the OCD-K33 fragile X chromosome was expansion of the CCG repeat at FRAXE. The number of the expanded repeats was estimated to be more than 300 copies, qualifying it as a full FRAXE mutation. Further analysis of the family members of OCD-K33 revealed another member with a full FRAXE mutation (630-1,200 copies of the CCG repeat), who had the clinical phenotype of speech impairment, and two other members with normal phenotypes and no FRAXE expansion. The two FRAXE expansions lead to complete methylation at the CCG repeat. The co-segregation of the full FRAXE mutation with apparent neurologic disorders in the same family provides further support to the notion that FRAXE is a genetic neurologic condition. Our findings expand the spectrum of clinical phenotypes associated with FRAXE mutations.

Chromosomes, Human, X↗

PubMed2003

Proteomic approach to coronary atherosclerosis shows ferritin light chain as a significant marker: evidence consistent with iron hypothesis in atherosclerosis.

Coronary artery disease (CAD) is the leading cause of mortality and morbidity in developed nations. We hypothesized that CAD is associated with distinct patterns of protein expression in the coronary arteries, and we have begun to employ proteomics to identify differentially expressed proteins in diseased coronary arteries. Two-dimensional (2-D) gel electrophoresis of proteins and subsequent mass spectrometric analysis identified the ferritin light chain as differentially expressed between 10 coronary arteries from patients with CAD and 7 coronary arteries from normal individuals. Western blot analysis indicated significantly increased expression of the ferritin light chain in the diseased coronary arteries (1.41 vs. 0.75; P = 0.01). Quantitative real-time PCR analysis showed that expression of ferritin light chain mRNA was decreased in diseased tissues (0.70 vs. 1.17; P = 0.013), suggesting that increased expression of ferritin light chain in CAD coronary arteries may be related to increased protein stability or upregulation of expression at the posttranscriptional level in the diseased tissues. Ferritin light chain protein mediates storage of iron in cells. We speculate that increased expression of the ferritin light chain may contribute to pathogenesis of CAD by modulating oxidation of lipids within the vessel wall through the generation of reactive oxygen species. Our results provide in situ proteomic evidence consistent with the "iron hypothesis," which proposes an association between excessive iron storage and a high risk of CAD. However, it is also possible that the increased ferritin expression in diseased coronary arteries is a consequence, rather than a cause, of CAD.

Adult↗

PubMed2003

Carnosic acid potentiates the antioxidant and prodifferentiation effects of 1alpha,25-dihydroxyvitamin D3 in leukemia cells but does not promote elevation of basal levels of intracellular calcium.

Differentiation therapy of cancer remains an only partially attained goal. Agents currently under active investigation include derivatives of vitamin D, modeled on its physiological hormone form, 1alpha,25-dihydroxyvitamin D(3) (1,25D(3)), but the calcemic effects of these compounds preclude their use in the clinic. An approach that may obviate this problem is to combine 1,25D(3) or its derivatives with other agents that increase the antineoplastic effects of low, nontoxic concentrations of vitamin D compounds. We have recently used the plant-derived polyphenolic antioxidant, carnosic acid (CA), to demonstrate an increase in the differentiating action of 1,25D(3) on human leukemia cells under these conditions (M. Danilenko et al., JNCI, 93: 1224-1233, 2001). We now show that treatment of HL60-G cells with either CA or 1,25D(3) alone resulted in a decrease in the intracellular levels of reactive oxygen species. Furthermore, the combination of 10 micro M CA and a low concentration of 1,25D(3) (1 nM) produced an enhanced antioxidant effect, which correlated with the potentiation of monocytic differentiation. Other plant antioxidants tested (curcumin, silibinin, and the organoselenium antioxidant ebselen) also potentiated differentiation induced by 1,25D(3), although alone, they had only minor differentiating effects. Differentiation induced by CA/1,25D(3) combinations was associated with increased intracellular glutathione content, whereas buthionine sulfoxime decreased both differentiation and the cellular glutathione content. This combination also enhanced the activation of the Raf-mitogen-activated protein/extracellular signal-regulated kinase kinase-extracellular signal-regulated kinase mitogen-activated protein kinase module and increased the binding of the activator protein-1 (AP-1) transcription factor to its cognate DNA element in the promoter regions of vitamin D receptor gene, suggesting that the mechanism of potentiation is at least in part attributable to induction and activation of components of this mitogen-activated protein kinase pathway. Cell treatment with a high concentration of 1,25D(3) (100 nM) resulted in a substantial elevation of basal intracellular calcium concentration. In contrast, importantly for an eventual clinical application of these studies, the potentiating action of CA on differentiation induced by a low concentration of 1,25D(3) (1 nM) was not accompanied by an elevation of basal intracellular calcium concentration. These findings suggest that combinations of CA with derivatives of vitamin D should be evaluated for use in differentiation therapy of myeloid leukemias.

Abietanes↗

PubMed2003

Alterations of anaphase-promoting complex genes in human colon cancer cells.

Ubiquitin-mediated proteolysis of cell cycle regulators is a major element of the cell cycle control. The anaphase-promoting complex (APC/C) is a large multisubunit ubiquitin-protein ligase required for the ubiquitination and degradation of G1 and mitotic checkpoint regulators. APC/C-dependent proteolysis regulates cyclin levels in G1, and triggers the separation of sister chromatids at the metaphase-anaphase transition and the destruction of mitotic cyclins at the end of mitosis. Furthermore, it was recently shown that APC/C regulates the degradation of crucial regulators of signal transduction pathways. We report here gene alterations in several components of this complex in human colon cancer cells, including APC6/CDC16 and APC8/CDC23 which are known to be key function elements. The experimental expression of a truncation mutant of APC8/CDC23 subunit (CDC23DeltaTPR) leads to abnormal levels of APC/C targets such as cyclin B1 and disturbs the cell cycle progression of colon epithelial cells through mitosis. Overall, these data support the hypothesis of a deleterious role of these mutations during colorectal carcinogenesis.

Anaphase-Promoting Complex-Cyclosome↗

PubMed2003

Hexamerization of p97-VCP is promoted by ATP binding to the D1 domain and required for ATPase and biological activities.

The 97-kDa valosin-containing protein (p97-VCP or VCP), a hexameric AAA ATPase, plays an important role in diverse cell activities, including ubiquitin-proteasome mediated protein degradation. In this report, we studied dissociation-reassembly kinetics to analyze the structure-function relationship in VCP. Urea-dissociated VCP can reassemble by itself, but addition of ATP, ADP, or ATP-gamma S accelerates the reassembly. Mutation in the ATP-binding site of D1, but not D2, domain abolishes the ATP acceleration effect and further delays the reassembly. Using hybrid hexamers of the wild type and ATP-binding site mutant, we show that hexameric structure and proper communication among the subunits are required for the ATPase activity and ubiquitin-proteasome mediated degradation. Thus, ATP-binding site in D1 plays a major role in VCP hexamerization, of which proper inter-subunit interaction is essential for the activities.

Adenosine Triphosphatases↗

PubMed2003

The role of invertases and hexose transporters in controlling sugar ratios in maternal and filial tissues of barley caryopses during early development.

To analyse carbohydrate metabolism and its role during early seed development of barley we characterised genes encoding two cell wall-bound invertases (HvCWINV1 and HvCWINV2) and two putative hexose transporter-like genes (HvSTP1 and HvSTP2). No typical vacuolar invertase gene could be identified. Instead, a gene encoding sucrose:fructan 6-fructosyltransferase (HvSF6FT1), an enzyme with soluble acid invertase activity, was isolated and characterised. Furthermore, enzyme activities and sugar levels were measured. HvSF6FT1-mRNA levels and acid soluble invertase activity are highest in the maternal pericarp 1-2 days after flowering (DAF). HvSF6FT1 is strongly expressed in regions flanking the main vascular bundle and to a lower extent in filial endospermal transfer cells, which persist until maturity and never accumulate starch. In contrast, cell wall-bound invertase HvCWINV2 is expressed early in development mainly in the style region and later on in pericarp areas which transiently accumulate starch and undergo degradation later in development. The hexose transporter HvSTP2 shows a temporal and spatial expression pattern similar to HvCWINV2. Transcripts of HvCWINV1 have been localised within the first row of endospermal cells and in the outermost area of the nucellar projection as well as in endospermal transfer cells before starch filling; the same regions of the endosperm are labelled with a hexose transporter HvSTP1-probe. HvSTP1 is expressed at very low levels within the pericarp but much higher in the syncytial endosperm at 3 DAF and in endospermal transfer cells 7 DAF. The temporal and spatial association of HvCWINV1 and HvSTP1 expression indicates that hexoses liberated by the invertase within the endospermal cavity are taken up by the transporter to be delivered into the central uncellularised space of the endosperm to supply mitotically active endosperm cells with hexoses. The results are discussed and compared with published data on the role of soluble sugars as signal molecules in seed developmental processes.

Carbohydrate Metabolism↗

PubMed2003

LQT4 gene: the "missing" ankyrin.

Mutations in ion channels have been implicated in the formation of long QT syndrome (LQTS). However, Mohler et al. have recently uncovered a role for ankyrin-B, a non-ion channel protein, in type IV LQTS. Calcium signalling is altered, and the functions of several channels and pumps that normally interact with wild-type ankyrin-B are impaired in the presence of mutant ankyrin-B. The authors suggest that by disrupting the functions of these channels, a new mechanism has been uncovered that can lead to cardiac myopathy.

Action Potentials↗

PubMed2003

[Preliminary study of p16 gene expression in pituitary adenomas].

BACKGROUND & OBJECTIVE: The inactivation and low expression of tumor suppressor gene p16 has been found to play an important role in the tumorigenesis of a wide variety of human tumors, but its association with human pituitary adenomas was not clear. This study was conducted to investigate the relationship between p16 gene expression and clinicopathologic features including invasiveness and recurrence in pituitary adenoma patients. METHODS: The p16 mRNA and p16 protein expression levels were examined using reverse transcription polymerase chain reaction (RT-PCR) and Western Blot analysis respectively in 70 pituitary adenomas and 10 normal brain tissues. RESULTS: Fifty-two of 70 (74.3%) tumor samples presented loss or low p16 mRNA and p16 protein. The invasive and recurrent adenomas had higher loss expression rates than noninvasive and nonrecurrent group respectively; however, there was no significant difference (P >0.05). Moreover, the mean diameter of adenomas without p16 expression was obviously larger than that of p16-positive tumors (22.1+/-7.2 mm versus 8.1+/-4.5 mm, P< 0.01). There was no association between p16 expression and other clinicopathologic features of pituitary adenomas. CONCLUSION: These findings suggested that p16 down-regulation may play an important role in the initial tumorigenesis, growth, and biological behavior of pituitary adenomas.

Adult↗

PubMed2003

[A study of PDE6B gene mutation and phenotype in Chinese cases with retinitis pigmentosa].

OBJECTIVE: To identify the mutation spectrum of phosphodiesterase beta subunit (PDE6B) gene, the incidence in Chinese patients with retinitis pigmentosa (RP) and their clinical phenotypic characteristics. METHODS: Screening of mutations within PDE6B gene was performed using polymerase chain reaction-heteroduplex-single strand conformation polymorphism (PCR-SSCP) and DNA sequence in 35 autosomal recessive (AR) RP and 55 sporadic RP cases. The phenotypes of the patients with the gene mutation were examined and analyzed. RESULTS: Novel complex heterozygous variants of PDE6B gene in a sporadic case, a T to C transversion in codon 323 resulting in the substitution of Gly by Ser and 2 base pairs (bp: G and T) insert between the 27th-28th bp upstream of the 5'-end of exon 10 were both present in a same isolate RP. But they are not found in 100 unrelated healthy individuals. Ocular findings showed diffuse pigmentary retinal degeneration in the midperipheral and peripheral fundi, optic atrophy and vessel attenuation. Multi-focal ERG indicated that the rod function was more severely deteriorated. A mutation was found in a case with RP in a ARRP family, a G to A transversion at 19th base upstream 5'-end of exon 11 (within intron 10) of PDE6B gene. A sporadic RP carried a sequence variant of PDE6B gene, a G to C transition, at the 15th base adjacent to the 3'-end of exon l8. In another isolate case with RP was found 2 bp (GT) insert between 31st and 32nd base upstream 5'-end of exon 4 (in intron 3) of PDE6B gene. CONCLUSIONS: There are novel complex heterozygous mutations of PDE6B gene responsible for a sporadic RP patient in China. This gene mutation associated with rod deterioration and RP. Several DNA variants were found in introns of PDE6B gene in national population.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed2003

[Screening gene mutations of the beta subunit of phosphodiesterase in the Chinese retinitis pigmentosa patients].

OBJECTIVE: To investigate the mutation spectrum of phosphodiesterase beta subunit (PDE6B) gene and incidence in Chinese retinitis pigmentosa (RP) patients. METHODS: Genomic DNA was extracted from the blood samples of 38 patients from 35 autosomal recessive retinitis pigmentosa (ARRP) families and 55 sporadic cases. The mutation of the PDE6B gene was detected using PCR-SSCP, and the amplified PCR product of abnormal bands was sequenced. RESULTS: Within intron 10 of PDE6B gene, a mutation was found in an ARRP family, a G --> A transition at 19th base upstream 5'-end of exon 11. A novel complex heterozygous variant of PDE6B gene in a sporadic case, a T to C transition in codon 323 resulting in the substitution of Gly by Ser and two bp(TG) inserted between the 27th-28th bp upstream of the 5'-end of exon 10 were both present in the same isolate RP. But they were not found in 100 unrelated normal individuals. A sporadic RP was found carrying a sequence variant of PDE6B gene, a G to C transversion in intron 18, the 15th base adjacent to the 3'end of exon 18. Another isolate RP was found to have 2 bp inserted between 31st and 32nd base upstream 5'end of exon 4 (in intron 3) of PDE6B gene. CONCLUSION: There is a complex heterozygous mutation of PDE6B gene responsible for a sporadic RP patient in China. Several DNA variants were found in intron of PDE6B gene in the national population.

Adult↗

PubMed2003

Mutation analysis of potassium channel genes KCNQ1 and KCNH2 in patients with long QT syndrome.

OBJECTIVE: To determine mutations of two common potassium channel subunit genes KCNQ1, KCNH2 causing long QT syndrome (LQTS) in the Chinese. METHODS: Thirty-one Chinese LQTS pedigrees were characterized for mutations in the two LQTS genes, KCNQ1 and KCNH2, by sequencing. RESULTS: Two novel KCNQ1 mutations, S277L in the S5 domain and G306V in the channel pore, and two novel KCNH2 mutations, L413P in the transmembrane domain S1 and L559H in the transmembrane domain S5 were identified. The triggering factors for cardiac events developed in these mutation carriers included physical exercise and excitation. Mutation L413P in KCNH2 was associated with the notched T wave on ECGs. Mutation L559H in KCNH2 was associated with the typical bifid T wave on ECGs. Mutation S277L in KCNQ1 was associated with a high-amplitude T wave and G306V was associated with a low-amplitude T wave. Two likely polymorphisms, IVS11 + 18C > T in KCNQ1 and L520V in KCNH2 were also identified in two LQTS patients. CONCLUSIONS: The mutation rates for both KCNQ1 (6.4%) and KCNH2 (6.4%) are lower in the Chinese population than those from North America or Europe.

Asian People↗

PubMed2003

[The causes and prevention of complications of radio frequency ablation treatment of primary and secondary liver cancers].

OBJECTIVE: To sum up causes and the prevention of complications after using the radio frequency ablation (RFA) to treat of primary and secondary liver cancers. METHODS: The clinical courses of 735 patients, undergoing percutaneous RFA treatment for a total of 1780 times were reviewed. The causes of the complications occurring after the RFA treatment, and their prevention and treatment were evaluated. RESULTS: Eleven complications after RFA treatment were found. Postoperative fever, sweating, and local pain were common. Serious complications, such as gut perforation, intraabdominal hemorrhage, and cardiovascular accident were found in 4 patients, and the mortality was 75%. CONCLUSIONS: The RFA treatment is an effective method for the treatment of primary and secondary liver tumor. Careful selection of patients, appropriate preoperative preparations, proper operative procedures, and suitable postoperative care are the key points in preventing the complications.

Adolescent↗

PubMed2002

Functional analysis of TBX5 missense mutations associated with Holt-Oram syndrome.

TBX5 is a T-box transcription factor that plays a critical role in organogenesis. Seven missense mutations in TBX5 have been identified in patients with Holt-Oram syndrome characterized by congenital heart defects and upper limb abnormalities. However, the functional significance and molecular pathogenic mechanisms of these mutations are not clear. In this study we describe functional defects in DNA binding, transcriptional activity, protein-protein interaction, and cellular localization of mutant TBX5 with these missense mutations (Q49K, I54T, G80R, G169R, R237Q, R237W, and S252I). Mutations G80R, R237Q, and R237W represent a group of mutations that dramatically reduce DNA-binding activity of TBX5, leading to reduced transcription activation by TBX5 and the loss of synergy in transcriptional activation between TBX5 and NKX2.5. The second group of mutations includes Q49K, I54T, G169R, and S252I, which have no or moderate effect on DNA-binding activity and the function of transcription activation of TBX5 but cause the complete loss of synergistic transcription activity between TBX5 and NKX2.5. All seven missense mutations greatly reduced the interaction of TBX5 with NKX2.5 in vivo and in vitro. Immunofluorescent staining showed that wild type TBX5 was localized completely into the nucleus, but mutants were localized in both nucleus and cytoplasm. These results demonstrate that all seven missense mutations studied here are functional mutations with a spectrum of defects ranging from decreases in DNA-binding activity and transcriptional activation to the dramatic reduction of interaction between TBX5 and NKX2.5, and loss of synergy in transcriptional activation between these two proteins, as well as impairment in the nuclear localization of TBX5. These defects are likely central to the pathogenesis of Holt-Oram syndrome.

Abnormalities, Multiple↗

PubMed2002

Localization of Nav1.5 sodium channel protein in the mouse brain.

Na(v)1.5 or SCN5A is a member of the voltage-dependent family of sodium channels. The distribution of Na(v)1.5 protein was investigated in the mouse brain using immunohistochemistry. Immunostaining with a Na(v)1.5-specific antibody revealed that Na(v)1.5 protein was localized in certain distinct regions of brain including the cerebral cortex, thalamus, hypothalamus, basal ganglia, cerebellum and brain stem. Notably, we found that Na(v)1.5 protein co-localized with neurofilaments and clustered at a high density in the neuronal processes, mainly axons. These results suggest that Na(v)1.5 protein may play a role in the physiology of the central nervous system (generation and propagation of electrical signals by axons).

Animals↗

PubMed2002

Neurofibromatosis type 1 gene as a mutational target in a mismatch repair-deficient cell type.

DNA mismatch repair (MMR) is the process by which incorrectly paired DNA nucleotides are recognized and repaired. A germline mutation in one of the genes involved in the process may be responsible for a dominantly inherited cancer syndrome, hereditary nonpolyposis colon cancer. Cancer progression in predisposed individuals results from the somatic inactivation of the normal copy of the MMR gene, leading to a mutator phenotype affecting preferentially repeat sequences (microsatellite instability, MSI). Recently, we identified children with a constitutional deficiency of MMR activity attributable to a mutation in the h MLH1 gene. These children exhibited a constitutional genetic instability associated with clinical features of de novo neurofibromatosis type 1 (NF1) and early onset of extracolonic cancer. Based on these observations, we hypothesized that somatic NF1 gene mutation was a frequent and possibly early event in MMR-deficient cells. To test this hypothesis, we screened for NF1 mutations in cancer cells. Genetic alterations were identified in five out of ten tumor cell lines with MSI, whereas five MMR-proficient tumor cell lines expressed a wild-type NF1 gene. Somatic NF1 mutations were also detected in two primary tumors exhibiting an MSI phenotype. Finally, a 35-bp deletion in the murine Nf1 coding region was identified in mlh1-/- mouse embryonic fibroblasts. These observations demonstrate that the NF1 gene is a mutational target of MMR deficiency and suggest that its inactivation is an important step of the malignant progression of MMR-deficient cells.

Adaptor Proteins, Signal Transducing↗

PubMed2002

ATPase activity of p97-valosin-containing protein (VCP). D2 mediates the major enzyme activity, and D1 contributes to the heat-induced activity.

The 97-kDa valosin-containing protein (p97-VCP) plays a role in a wide variety of cellular activities, many of which are regulated by the ubiquitin-proteasome (Ub-Pr)-mediated degradation pathway. We previously demonstrated that VCP binds to multi-ubiquitin chains and may act as a molecular chaperone that targets the ubiquitinated substrates to the proteasome for degradation. In this report, we show that although the ubiquitin chain-binding activity, carried out by the N-terminal 200 residues (N domain), is necessary for the degradation of proteasome substrates, it is not sufficient. Using in vitro degradation assays, we demonstrated that the entire VCP molecule, consisting of the N domain and two ATPase domains D1 and D2, is required for mediating the Ub-Pr degradation. The ATPase activity of VCP requires Mg(2+), and is stimulated by high temperature. Under optimal conditions, VCP hydrolyzes ATP with a K(m) of approximately 0.33 mm and a V(max) of approximately 0.52 nmol P(i) min(-1) microg(-1). At a physiological temperature, mutation in D2 significantly inhibits the ATPase activity, while that in D1 has little effect. Interestingly, mutations in D1, but not D2, abolish the heat-stimulated ATPase activity. Thus, we provide the first demonstration that the ATPase activity of VCP is required for mediating the Ub-Pr degradation, that D2 accounts for the major ATPase activity, and that D1 contributes to the heat-induced activity.

Adenosine Triphosphatases↗

PubMed2002

Ataxia and paroxysmal dyskinesia in mice lacking axonally transported FGF14.

Fibroblast growth factor 14 (FGF14) belongs to a distinct subclass of FGFs that is expressed in the developing and adult CNS. We disrupted the Fgf14 gene and introduced an Fgf14(N-beta-Gal) allele that abolished Fgf14 expression and generated a fusion protein (FGF14N-beta-gal) containing the first exon of FGF14 and beta-galactosidase. Fgf14-deficient mice were viable, fertile, and anatomically normal, but developed ataxia and a paroxysmal hyperkinetic movement disorder. Neuropharmacological studies showed that Fgf14-deficient mice have reduced responses to dopamine agonists. The paroxysmal hyperkinetic movement disorder phenocopies a form of dystonia, a disease often associated with dysfunction of the putamen. Strikingly, the FGF14N-beta-gal chimeric protein was efficiently transported into neuronal processes in the basal ganglia and cerebellum. Together, these studies identify a novel function for FGF14 in neuronal signaling and implicate FGF14 in axonal trafficking and synaptosomal function.

Animals↗