Pantakani, Dasaradha Venkata Krishna

[["dc.bibliographiccitation.firstpage","99"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","European Journal of Neurology"],["dc.bibliographiccitation.lastpage","105"],["dc.bibliographiccitation.volume","18"],["dc.contributor.author","Klimpe, Sven"],["dc.contributor.author","Zibat, Arne"],["dc.contributor.author","Zechner, Ulrich"],["dc.contributor.author","Wellek, B."],["dc.contributor.author","Shoukier, Moneef"],["dc.contributor.author","Sauter, Simone M."],["dc.contributor.author","Pantakani, Dasaradha Venkata Krishna"],["dc.contributor.author","Mannan, Ashraf U."],["dc.date.accessioned","2018-11-07T09:01:10Z"],["dc.date.available","2018-11-07T09:01:10Z"],["dc.date.issued","2011"],["dc.description.abstract","Background: Mutations in the SPG4/SPAST gene are the most common cause for hereditary spastic paraplegia (HSP). The splice-site mutations make a significant contribution to HSP and account for 17.4% of all types of mutations and 30.8% of point mutations in the SPAST gene. However, only few studies with limited molecular approach were conducted to investigate and decipher the role of SPAST splice-site mutations in HSP. Methods: A reverse transcriptase-polymerase chain reaction (RT-PCR) analysis and quantitative allele-specific expression assay were performed. Results: We have characterized the consequence of two novel splice-site mutations (c.1493 + 1G > A and c.1414-1G > A) in the SPAST gene in two different families with pure HSP. The RT-PCR analysis revealed that both spastin mutations are indeed splice-site mutations and cause skipping of exon 12. Furthermore, RT-PCR data suggested that these splice-site mutations may cause leaky splicing. By means of a quantitative allele-specific expression assay, we could confirm that both splice-site mutations cause leaky splicing, as the relative expression of the exon 12-skipped transcript was reduced (21.1 +/- 3.6 compared to expected 50%). Conclusions: Our finding supports a \"threshold-effect-model\" for functional spastin in HSP. A higher level (78.8 +/- 3.9%) of functional spastin than the expected ratio of 50% owing to leaky splicing might cause late age at onset of HSP. Remarkably, we could show that a quantitative allele-specific expression assay is a simple and effective tool to evaluate the role of most types of spastin splice-site mutations in HSP."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft; Institute internal fund"],["dc.identifier.doi","10.1111/j.1468-1331.2010.03079.x"],["dc.identifier.isi","000285356300015"],["dc.identifier.pmid","20491894"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/24351"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell Publishing, Inc"],["dc.relation.issn","1351-5101"],["dc.title","Evaluating the effect of spastin splice mutations by quantitative allele-specific expression assay"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","268"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Clinical Genetics"],["dc.bibliographiccitation.lastpage","272"],["dc.bibliographiccitation.volume","73"],["dc.contributor.author","Pantakani, Dasaradha Venkata Krishna"],["dc.contributor.author","Zechner, Ulrich"],["dc.contributor.author","Arygriou, L."],["dc.contributor.author","Pauli, Silke"],["dc.contributor.author","Sauter, Simone M."],["dc.contributor.author","Mannan, Ashraf U."],["dc.date.accessioned","2018-11-07T11:17:25Z"],["dc.date.available","2018-11-07T11:17:25Z"],["dc.date.issued","2008"],["dc.description.abstract","The SPG4 gene is frequently mutated in autosomal dominant form of hereditary spastic paraplegia (HSP). We report that the compound heterozygous sequence variants S44L, a known polymorphism, and c.1687G > A, a novel mutation in SPG4 cause a severe form of HSP in a patient. The family members carrying solely c.1687G > A mutation are asymptomatic for HSP. The reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed that the c.1687G > A mutation is a splice site mutation and causes skipping of the exon 15 of spastin. Furthermore, quantification of RT-PCR products by sequencing and quantification of allele-specific expression by pyrosequencing assay revealed that c.1687G > A is a leaky or hypomorphic splice site mutation. At the protein level, c.1687G > A mutation in SPG4 leads to E563K substitution. In ex vivo study, about 10% of cells expressing E563K mutant spastin showed filamentous expression pattern, suggesting a hypomorphic effect at the protein level. Collectively, our results suggest that S44L in association with c.1687G > A (E563K) drops the functional level of spastin below a threshold limit sufficient to manifest HSP."],["dc.identifier.doi","10.1111/j.1399-0004.2007.00953.x"],["dc.identifier.isi","000252929000012"],["dc.identifier.pmid","18190593"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/54802"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Blackwell Publishing"],["dc.relation.issn","0009-9163"],["dc.title","Compound heterozygosity in the SPG4 gene causes hereditary spastic paraplegia"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","613"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Journal of Neurochemistry"],["dc.bibliographiccitation.lastpage","624"],["dc.bibliographiccitation.volume","106"],["dc.contributor.author","Pantakani, Dasaradha Venkata Krishna"],["dc.contributor.author","Swapna, Lakshmipuram S."],["dc.contributor.author","Srinivasan, Narayanaswamy"],["dc.contributor.author","Mannan, Ashraf U."],["dc.date.accessioned","2018-11-07T11:13:37Z"],["dc.date.available","2018-11-07T11:13:37Z"],["dc.date.issued","2008"],["dc.description.abstract","Spastin, a member of the ATPases associated with various cellular activities (AAA) family of proteins, is the most frequently mutated in hereditary spastic paraplegia. The defining feature of the AAA proteins is a structurally conserved AAA domain which assembles into an oligomer. By chemical cross-linking and gel filtration chromatography, we show that spastin oligomerizes into a hexamer. Furthermore, to gain a comprehensive overview of the oligomeric structure of spastin, we generated a structural model of the AAA domain of spastin using template structure of VPS4B and p97/VCP. The generated model of spastin provided us with a framework to classify the identified missense mutations in the AAA domain from hereditary spastic paraplegia patients into different structural/functional groups. Finally, through co-localization studies in mammalian cells, we show that E442Q mutant spastin acts in a dominant negative fashion and causes redistribution of both wild-type spastin monomer and spastin interacting protein, RTN1 into filamentous microtubule bundles."],["dc.identifier.doi","10.1111/j.1471-4159.2008.05414.x"],["dc.identifier.isi","000257708000011"],["dc.identifier.pmid","18410514"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/53940"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Blackwell Publishing"],["dc.relation.issn","0022-3042"],["dc.title","Spastin oligomerizes into a hexamer and the mutant spastin (E442Q) redistribute the wild-type spastin into filamentous microtubule"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","617"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Human Mutation"],["dc.bibliographiccitation.lastpage","621"],["dc.bibliographiccitation.volume","31"],["dc.contributor.author","Bonn, Florian"],["dc.contributor.author","Pantakani, Krishna"],["dc.contributor.author","Shoukier, Moneef"],["dc.contributor.author","Langer, Thomas"],["dc.contributor.author","Mannan, Ashraf U."],["dc.date.accessioned","2018-11-07T08:43:34Z"],["dc.date.available","2018-11-07T08:43:34Z"],["dc.date.issued","2010"],["dc.description.abstract","An autosomal recessive form of hereditary spastic paraplegia (AR-HSP) is primarily caused by mutations in the SPG7 gene, which codes for paraplegin, a subunit of the hetero-oligomeric m-AAA protease in mitochondria. In the current study, sequencing of the SPG7 gene in the genomic DNA of 25 unrelated HSP individuals/families led to the identification of two HSP patients with compound heterozygous mutations (p.G349S/p.W583C and p.A510V/p.N739KfsX741) in the coding sequence of the SPG7 gene. We used a yeast complementation assay to evaluate the functional consequence of novel SPG7 sequence variants detected in the HSP patients. We assessed the proteolytic activity of hetero-oligomeric m-AAA proteases composed of paraplegin variant(s) and proteolytically inactive forms of AFG3L2 (AFG3L2(E575Q) or AFG3L2(K354A)) upon expression in m-AAA protease-deficient yeast cells. We demonstrate that the newly identified paraplegin variants perturb the proteolytic function of hetero-oligomeric m-AAA protease. Moreover, commonly occurring silent polymorphisms such as p.T503A and p.R688Q could be distinguished from mutations (p.G349S, p.W583C, p.A510V, and p.N739KfsX744) in our HSP cohort. The yeast complementation assay thus can serve as a reliable system to distinguish a pathogenic mutation from a silent polymorphism for any novel SPG7 sequence variant, which will facilitate the interpretation of genetic data for SPG7. Hum Mutat 31:617-621, 2010. (C) 2010 Wiley-Liss, Inc."],["dc.identifier.doi","10.1002/humu.21226"],["dc.identifier.isi","000277779100013"],["dc.identifier.pmid","20186691"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6230"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/20000"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-liss"],["dc.relation.issn","1059-7794"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Functional Evaluation of Paraplegin Mutations by a Yeast Complementation Assay"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e29584"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","PLOS ONE"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Pantakani, D. V. Krishna"],["dc.contributor.author","Czyzewska, Marta M."],["dc.contributor.author","Sikorska, Anna"],["dc.contributor.author","Bodda, Chiranjeevi"],["dc.contributor.author","Mannan, Ashraf U."],["dc.date.accessioned","2018-11-07T08:48:45Z"],["dc.date.available","2018-11-07T08:48:45Z"],["dc.date.issued","2011"],["dc.description.abstract","ZFYVE27 (Protrudin) was originally identified as an interacting partner of spastin, which is most frequently mutated in hereditary spastic paraplegia. ZFYVE27 is a novel member of FYVE family, which is implicated in the formation of neurite extensions by promoting directional membrane trafficking in neurons. Now, through a yeast two-hybrid screen, we have identified that ZFYVE27 interacts with itself and the core interaction region resides within the third hydrophobic region (HR3) of the protein. We confirmed the ZFYVE27's self-interaction in the mammalian cells by co-immunoprecipitation and co-localization studies. To decipher the oligomeric nature of ZFYVE27, we performed sucrose gradient centrifugation and showed that ZFYVE27 oligomerizes into dimer/tetramer forms. Sub-cellular fractionation and Triton X-114 membrane phase separation analysis indicated that ZFYVE27 is a peripheral membrane protein. Furthermore, ZFYVE27 also binds to phosphatidylinositol 3-phosphate lipid moiety. Interestingly, cells expressing ZFYVE27(Delta HR3) failed to produce protrusions instead caused swelling of cell soma. When ZFYVE27(Delta HR3) was co-expressed with wild-type ZFYVE27 (ZFYVE27(WT)), it exerted a dominant negative effect on ZFYVE27(WT) as the cells co-expressing both proteins were also unable to induce protrusions and showed cytoplasmic swelling. Altogether, it is evident that a functionally active form of oligomer is crucial for ZFYVE27 ability to promote neurite extensions."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft [MA 3344-2]"],["dc.identifier.doi","10.1371/journal.pone.0029584"],["dc.identifier.isi","000300676300068"],["dc.identifier.pmid","22216323"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8210"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/21300"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 2.5"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.5"],["dc.title","Oligomerization of ZFYVE27 (Protrudin) Is Necessary to Promote Neurite Extension"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","187"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","European Journal of Human Genetics"],["dc.bibliographiccitation.lastpage","194"],["dc.bibliographiccitation.volume","17"],["dc.contributor.author","Shoukier, Moneef"],["dc.contributor.author","Neesen, Juergen"],["dc.contributor.author","Sauter, Simone M."],["dc.contributor.author","Argyriou, Loukas"],["dc.contributor.author","Doerwald, Nadine"],["dc.contributor.author","Pantakani, Dasaradha Venkata Krishna"],["dc.contributor.author","Mannan, Ashraf U."],["dc.date.accessioned","2018-11-07T08:32:59Z"],["dc.date.available","2018-11-07T08:32:59Z"],["dc.date.issued","2009"],["dc.description.abstract","The SPAST gene encoding for spastin plays a central role in the genetically heterogeneous group of diseases termed hereditary spastic paraplegia (HSP). In this study, we attempted to expand and refine the genetic and phenotypic characteristics of SPAST associated HSP by examining a large cohort of HSP patients/families. Screening of 200 unrelated HSP cases for mutations in the SPAST gene led to detection of 57 mutations (28.5%), of which 47 were distinct and 29 were novel mutations. The distribution analysis of known SPAST mutations over the structural domains of spastin led to the identification of several regions where the mutations were clustered. Mainly, the clustering was observed in the AAA (ATPases associated with diverse cellular activities) domain; however, significant clustering was also observed in the MIT (microtubule interacting and trafficking), MTBD (microtubule-binding domain) and an N-terminal region (228-269 residues). Furthermore, we used a previously generated structural model of spastin as a framework to classify the missense mutations in the AAA domain from the HSP patients into different structural/functional groups. Our data also suggest a tentative genotype-phenotype correlation and indicate that the missense mutations could cause an earlier onset of the disease."],["dc.identifier.doi","10.1038/ejhg.2008.147"],["dc.identifier.isi","000262499600010"],["dc.identifier.pmid","18701882"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/17465"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","1018-4813"],["dc.title","Expansion of mutation spectrum, determination of mutation cluster regions and predictive structural classification of SPAST mutations in hereditary spastic paraplegia"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]