HIP-I: A huntingtin interacting protein isolated by the yeast two-hybrid system

Wanker, Erich E.; Rovira, Carlos; Scherzinger, Eberhard; Hasenbank, Renate; Wälter, Stephanie; Tait, Danilo; Colicelli, John; Lehrach, Hans

doi:10.1093/hmg/6.3.487

Cited by 309 publications

(212 citation statements)

References 34 publications

Supporting

Mentioning

207

Contrasting

Order By: Relevance

“…Although there is some controversy about the role of htt aggregates, many authors propose, on the basis that Htt interacts with proteins associated to cytoskeleton-based transport (Li et al 1995;Kalchman et al 1997;Wanker et al 1997;Li et al 1998), that their presence in the neuropil is implicated in disturbances of axonal transport (Li et al 2001). Our present findings show that decreasing BDNF expression in the R6/1 mouse line increases the number of non-nuclear aggregates, which could be related to the enhanced dysfunction of dopaminergic neurons in bDM mice.…”

Section: Discussionsupporting

confidence: 51%

Brain‐derived neurotrophic factor modulates dopaminergic deficits in a transgenic mouse model of Huntington's disease

Pineda¹,

Canals²,

Bosch³

et al. 2005

Journal of Neurochemistry

View full text Add to dashboard Cite

Dysfunction of dopaminergic neurons may contribute to motor impairment in Huntington's disease. Here, we study the role of brain-derived neurotrophic factor (BDNF) in alterations of the nigrostriatal system associated with transgenics carrying mutant huntingtin. Using huntingtin-BDNF +/-double-mutant mice, we analyzed the effects of reducing the levels of BDNF expression in a model of Huntington's disease (R6/1). When compared with R6/1 mice, these mice exhibit an increased number of aggregates in the substantia nigra pars compacta. In addition, reduction of BDNF expression exacerbates the dopaminergic neuronal dysfunction seen in mutant huntingtin mice, such as the decrease in retrograde labelling of dopaminergic neurons and striatal dopamine content. However, mutant huntingtin mice with normal or lowered BDNF expression show the same decrease in the anterograde transport, number of dopaminergic neurons and nigral volume. In addition, reduced BDNF expression causes decreased dopamine receptor expression in mutant huntingtin mice. Examination of changes in locomotor activity induced by dopamine receptor agonists revealed that, in comparison with R6/1 mice, the double mutant mice exhibit lower activity in response to amphetamine, but not to apomorphine. In conclusion, these findings demonstrate that the decreased BDNF expression observed in Huntington's disease exacerbates dopaminergic neuronal dysfunction, which may participate in the motor disturbances associated with this neurodegenerative disorder. Keywords: amphetamine, axonal transport, movement disorders, neuronal dysfunction, neurotrophins, substantia nigra. J. Neurochem. (2005Neurochem. ( ) 93, 1057Neurochem. ( -1068 Neurodegenerative disorders are characterized by a progressive and specific loss of neurons. Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative disorder caused by unstable expanded CAG repeats in the 5¢-coding region of the huntingtin (htt) gene (The Huntington's Disease Collaborative Research Group 1993). The primary brain region affected in HD is the striatum, where a selective degeneration of GABAergic projection neurons occurs. However, neuronal degeneration also extends to other brain areas, including the cerebral cortex, substantia nigra (SN), globus pallidus and subthalamic nucleus as the disease progresses (Rubinsztein 2002;Browne and Beal 2004).The important role of the SN dopaminergic system in the control of motor function suggests that dysfunctional dopaminergic transmission may play a role in motor disturbances, the most common feature of HD (Hickey et al. 2002). In fact, reduced expression of dopamine receptors and Received August 6, 2004; revised manuscript received December 10, 2004; accepted December 14, 2004. Address correspondence and reprint requests to Dr J. Alberch, Departament de Biologia CelAElular i Anatomia Patològica, Facultat de Medicina, Universitat de Barcelona, C/Casanova, 143 E-08036 Barcelona, Spain. E-mail: alberch@ub.eduAbbreviations used: BDA, biotinylated dextran am...

show abstract

Section: Discussionsupporting

confidence: 51%

Brain‐derived neurotrophic factor modulates dopaminergic deficits in a transgenic mouse model of Huntington's disease

Pineda¹,

Canals²,

Bosch³

et al. 2005

Journal of Neurochemistry

View full text Add to dashboard Cite

show abstract

“…[12][13][14][15][16] In several cases, the strength of Htt protein interactions has been shown to be affected by the length of polyQ tract, including the interaction with CREB binding protein, 7,9 HAP-1, 17 nuclear receptor co-repressor N-CoR, 18 Sp1 19 and others. 20,21 Rhes, a striatal-specific guanine nucleotide-binding protein, interacts preferentially with polyQ-expanded Htt and induces its sumoylation, leading to cytotoxicity.…”

Section: Resultsmentioning

confidence: 99%

Huntingtin protein interactions altered by polyglutamine expansion as determined by quantitative proteomic analysis

et al. 2012

View full text Add to dashboard Cite

“…The plasmid pBTM-CAG20 is described elsewhere. 76 Plasmid pTL1-HA-ATX2-FD was obtained by subcloning an EcoRI/KpnI fragment isolated from pBTM-ATX2-FD into the corresponding sites of vector pTL1-HA. Inserting a SalI/NotI fragment from pGAD-PABC into the XhoI/NotI sites of vector pTL-Flag generated plasmid pTL-FLAG-PABC.…”

Section: Plasmidsmentioning

confidence: 99%

An Integrative Approach to Gain Insights into the Cellular Function of Human Ataxin-2

Ralser

Albrecht

Nonhoff

et al. 2005

Journal of Molecular Biology

135

145

View full text Add to dashboard Cite

Spinocerebellar ataxia type 2 (SCA2) is a hereditary neurodegenerative disorder caused by a trinucleotide expansion in the SCA2 gene, encoding a polyglutamine stretch in the gene product ataxin-2 (ATX2), whose cellular function is unknown. However, ATX2 interacts with A2BP1, a protein containing an RNA-recognition motif, and the existence of an interaction motif for the C-terminal domain of the poly(A)-binding protein (PABC) as well as an Lsm (Like Sm) domain in ATX2 suggest that ATX2 like its yeast homolog Pbp1 might be involved in RNA metabolism. Here, we show that, similar to Pbp1, ATX2 suppresses the petite (pet K ) phenotype of Dmrs2 yeast strains lacking mitochondrial group II introns. This finding points to a close functional relationship between the two homologs. To gain insight into potential functions of ATX2, we also generated a comprehensive protein interaction network for Pbp1 from publicly available databases, which implicates Pbp1 in diverse RNA-processing pathways. The functional relationship of ATX2 and Pbp1 is further corroborated by the experimental confirmation of the predicted interaction of ATX2 with the cytoplasmic poly(A)-binding protein 1 (PABP) using yeast-2-hybrid analysis as well as co-immunoprecipitation experiments. Immunofluorescence studies revealed that ATX2 and PABP co-localize in mammalian cells, remarkably, even under conditions in which PABP accumulates in distinct cytoplasmic foci representing sites of mRNA triage.

show abstract

HIP-I: A huntingtin interacting protein isolated by the yeast two-hybrid system

Cited by 309 publications

References 34 publications

Brain‐derived neurotrophic factor modulates dopaminergic deficits in a transgenic mouse model of Huntington's disease

Brain‐derived neurotrophic factor modulates dopaminergic deficits in a transgenic mouse model of Huntington's disease

Huntingtin protein interactions altered by polyglutamine expansion as determined by quantitative proteomic analysis

An Integrative Approach to Gain Insights into the Cellular Function of Human Ataxin-2

Contact Info

Product

Resources

About