Molecular Cloning of a Novel 130-kDa Cytoplasmic Protein, Ankhzn, Containing Ankyrin Repeats Hooked to a Zinc Finger Motif

Ito, Kenjiro; Ishii, Naoya; Miyashita, Akinori; Tominaga, Kei; Kuriyama, Hideyuki; Maruyama, Hiroshi; Shirai, Makoto; Naito, Makoto; Arakawa, Masaaki; Kuwano, Ryozo

doi:10.1006/bbrc.1999.0430

Cited by 15 publications

(10 citation statements)

References 30 publications

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“…In 2007, three genes located on human chromosome 17p13, ANKFY1 , ARRB2 and KIF1C , were reported to be associated with ARSACS (Bouslam et al., 2007). Ankfy1 is ubiquitously expressed in human tissues (Ito et al, 1999). In situ hybridization revealed that the Ankfy1 mRNA was expressed in the spinal cord from the embryonic to postnatal stages, the hippocampus and particularly the cerebellum (Figure 1A).…”

Section: Resultsmentioning

confidence: 99%

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Purkinje Cell Degeneration and Motor Coordination Deficits in a New Mouse Model of Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay

Ding

Weng

Fan

et al. 2017

Front. Mol. Neurosci.

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Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an early-onset neurodegenerative disorder. In 2007, a novel locus, SAX2, which is located on chromosome 17p13 and contains 3 genes, ankyrin repeat and FYVE domain-containing 1 (ANKFY1), β-arrestin 2 (ARRB2) and kinesin family member 1C (KIF1C), was linked to ARSACS. We generated Ankfy1 heterozygous (Ankfy1/+) mice to establish an animal model and examine the pathophysiological basis of ARSACS. The transgenic mice displayed an abnormal gait with progressive motor and cerebellar nerve dysfunction that was highly reminiscent of ARSACS. These clinical features were accompanied by an early-onset and progressive loss of Purkinje cells, followed by gliosis. Additionally, the loss of Ankfy1 function resulted in an abnormal expression of neurotrophic factors (NTFs) in the Ankfy1/+ mouse cerebellum. Moreover, Purkinje cells cultured from neonatal Ankfy1/+ mice exhibited a shorter dendritic length and decreased numbers of dendritic spines. Importantly, cerebellar Purkinje cells from Ankfy1/+ mice and cells transfected with a lentiviral Ankfy1 shRNA underwent apoptosis. We propose that transgenic Ankfy1/+ mice are a useful model for studying the pathogenesis of ARSACS and for exploring the molecular mechanisms involved in this neurodegenerative disease.

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Section: Resultsmentioning

confidence: 99%

“…The ANKFY1 gene was first described by Ito et al (1999). The human ANKFY1 gene encodes Ankfy1, a multimodular protein consisting of 1166 amino acids that exhibits 84.9% identity to the mouse homolog, which is highly expressed in the adult brain and spinal cord (Kuriyama et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Purkinje Cell Degeneration and Motor Coordination Deficits in a New Mouse Model of Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay

Ding

Weng

Fan

et al. 2017

Front. Mol. Neurosci.

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“…Similar to GAPVD1, ANKFY1 interacts with RAB5, serving as a versatile RAB5 effector. [72][73][74][75] The identified mutation (p.Arg95Leu) is conserved to D. melanogaster and locates within a homozygosity peak that is shared between both siblings (Supplemental Figure 2, C and D). Renal biopsy revealed FSGS ( Figure 1H).…”

Section: Mutations In Gapvd1 and Ankfy1 Two Rab5 Interactors In Fammentioning

confidence: 99%

GAPVD1 and ANKFY1 Mutations Implicate RAB5 Regulation in Nephrotic Syndrome

Hermle

Schneider

Schapiro

et al. 2018

JASN

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“…This view is supported by the observation that the majority of the characterized mammalian FYVE domain proteins including Ankhzn (16), DFCP1 (17), EEA1 (3), Rabenosyn-5 (9), Rabip4 (10), and SARA (15) are localized in early endosomes or vesicular structures in the cell. Of these proteins, the FYVE domain of Rabenosyn-5 is clearly demonstrated to be sufficient to target the protein to endosomal membranes (10).…”

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confidence: 92%

Endofin, an Endosomal FYVE Domain Protein

Seet

Hong

2001

Journal of Biological Chemistry

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KIAA0305 is an uncharacterized member of the FYVE domain protein family. It is closely related to SARA, with about 50% identity in the carboxyl-terminal 800-amino acid region. Indirect immunofluorescence microscopy using polyclonal antibodies raised against KIAA0305 revealed that it is enriched in early endosomes. The Myc-tagged version is also faithfully targeted to the early endosome. We have tentatively called KIAA0305 endofin (for endosome-associated FYVE-domain protein). The association of endofin with endosomes is mediated by its FYVE domain because deletion mutants lacking the central FYVE finger motif are distributed in the cytoplasm. In addition, a single point mutation in the FYVE finger motif at cysteine residue 753 (C753S) is sufficient to abolish its endosomal association. Its endosomal localization is also sensitive to the phosphatidylinositol 3-kinase inhibitor, wortmannin. Using in vitro liposome binding assays, we demonstrate that Myc-tagged endofin associates preferentially with phosphatidylinositol 3-phosphate, whereas the C753S point mutant was unable to do so. We also show that endofin co-localizes with SARA but that they are not associated in a common complex because they failed to co-immunoprecipitate in co-expressing cells. Endofin also does not associate with Smad2 nor behave like SARA in affecting transforming growth factor-␤ signaling. At high levels of expression, both endofin and SARA can cause an endosome aggregation/fusion effect. In COS7 cells, which can support high levels of exogenous protein expression, both proteins can also cause other structural anomalies in the endocytic pathway, as represented by enlarged vesicular structures. These endosomal aggregates/fusions accumulated endocytosed epidermal growth factor. Taken together, this report provides evidence to suggest that endofin and the highly related SARA are endosomal proteins with potential roles in regulating membrane traffic.

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Molecular Cloning of a Novel 130-kDa Cytoplasmic Protein, Ankhzn, Containing Ankyrin Repeats Hooked to a Zinc Finger Motif

Cited by 15 publications

References 30 publications

Purkinje Cell Degeneration and Motor Coordination Deficits in a New Mouse Model of Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay

Purkinje Cell Degeneration and Motor Coordination Deficits in a New Mouse Model of Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay

GAPVD1 and ANKFY1 Mutations Implicate RAB5 Regulation in Nephrotic Syndrome

Endofin, an Endosomal FYVE Domain Protein

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