A clinical, genetic, and neuropathologic study in a family with 16q-linked ADCA type III

Owada, Kiyoshi; Ishikawa, Kinya; Toru, Shuta; Ishida, Gen; Gomyoda, Manabu; Tao, O.; Noguchi, Yoshihiro; Kitamura, Keiko; Kondo, Ikuko; Noguchi, Eitaro; Arinami, Tadao; Mizusawa, Hidehiro

doi:10.1212/01.wnl.0000173065.75680.e2

Cited by 69 publications

(92 citation statements)

References 8 publications

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“…Curiously, mutations found in several forms of congenital neurological disorders such as spinocerebellar ataxia type 4 (24 -26) and autosomal dominant cerebellar ataxia (27)(28)(29) have been mapped to chromosome 16q22.1, a region containing NHE5. However, much remains unknown as to the molecular regulation of NHE5 and its role in brain function.…”

mentioning

confidence: 99%

Secretory Carrier Membrane Protein 2 Regulates Cell-surface Targeting of Brain-enriched Na+/H+ Exchanger NHE5

Diering

Church

Numata

2009

Journal of Biological Chemistry

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NHE5 is a brain-enriched Na ؉ /H؉ exchanger that dynamically shuttles between the plasma membrane and recycling endosomes, serving as a mechanism that acutely controls the local pH environment. In the current study we show that secretory carrier membrane proteins (SCAMPs), a group of tetraspanning integral membrane proteins that reside in multiple secretory and endocytic organelles, bind to NHE5 and co-localize predominantly in the recycling endosomes. In vitro protein-protein interaction assays revealed that NHE5 directly binds to the N-and C-terminal cytosolic extensions of SCAMP2. Heterologous expression of SCAMP2 but not SCAMP5 increased cell-surface abundance as well as transporter activity of NHE5 across the plasma membrane. Expression of a deletion mutant lacking the SCAMP2-specific N-terminal cytosolic domain, and a mini-gene encoding the N-terminal extension, reduced the transporter activity. Although both Arf6 and Rab11 positively regulate NHE5 cell-surface targeting and NHE5 activity across the plasma membrane, SCAMP2-mediated surface targeting of NHE5 was reversed by dominant-negative Arf6 but not by dominant-negative Rab11. Together, these results suggest that SCAMP2 regulates NHE5 transit through recycling endosomes and promotes its surface targeting in an Arf6-dependent manner.

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mentioning

confidence: 99%

Secretory Carrier Membrane Protein 2 Regulates Cell-surface Targeting of Brain-enriched Na+/H+ Exchanger NHE5

Diering

Church

Numata

2009

Journal of Biological Chemistry

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“…Thus, DPN in SCA6 is considered to be due to a dysfunction of vVOR cancellation. The detailed analyses of these neuropathological changes in the flocculus of SCA31 have not yet been done [1,4,16]. Future studies should consider vVOR in SCA6 and SCA31.…”

Section: Discussionmentioning

confidence: 99%

Rare frequency of downbeat positioning nystagmus in spinocerebellar ataxia type 31

Yabe

Matsushima

Yoshida

et al. 2015

Journal of the Neurological Sciences

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Spinocerebellar ataxia type 31 (SCA31) and spinocerebellar ataxia type 6 (SCA6) are the most frequent types of spinocerebellar degeneration in Japan. Previous reports described that it was difficult to distinguish SCA6 and SCA31 in clinical situations. There is not much difference except that the onset age of SCA31 is slightly higher than that of SCA6. Therefore we surveyed our medical records retrospectively, and then compared clinical symptoms of SCA6 and SCA31. As previously stated, the onset age of SCA31 is higher than that of SCA6. Gaze-evoked nystagmus is more frequent in SCA6 than in SCA31. The percentage in downbeat positioning nystagmus (DPN) is as high as 63% in SCA6. In contrast, DPN in SCA31 is rare and subtle. Our study suggests that the presence of DPN is an important sign that can differentiate SCA6 from SCA31 clinically.

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“…The pathogenesis of gaze-evoked nystagmus has been discussed in association with the lesions pathologically involved [30]. Purkinje cell degeneration is the most prominent pathological finding in both SCA6 and 16q-ADCA [30,31]. The difference in the frequency in gaze-evoked nystagmus between SCA6 and 16q-ADCA may be due to the difference of the degree and distribution of affected lesions between both diseases.…”

Section: Discussionmentioning

confidence: 99%

Severity and Progression Rate of Cerebellar Ataxia in 16q-linked Autosomal Dominant Cerebellar Ataxia (16q-ADCA) in the Endemic Nagano Area of Japan

et al. 2008

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ABSTRACT16q22.1-linked autosomal dominant cerebellar ataxia (16q-ADCA) is a recently defined subtype of ADCA identified by a disease-specific C/T substitution in the 5'-UTR of the puratrophin-1 gene. In Nagano, the central mountainous district of the main island of Japan, 16q-ADCA and spinocerebellar ataxia type 6 (SCA6) are the most and second most prevalent subtypes of ADCA, respectively. Both subtypes are classified into Harding's ADCAIII, but little attention has been given to the differences in the severity and progression rate of cerebellar ataxia between 16q-ADCA and SCA6. We investigated the clinical severity and progression rate of cerebellar ataxia of 16q-ADCA patients using ICARS and SARA, and compared them with those of SCA6 patients. The age at onset was much higher in 16q-ADCA patients (60.1 ± 9.8 years, n = 66) than in SCA6 patients (41.1 ± 8.7 years, n = 35). Clinical features of 16q-ADCA were basically consistent with pure cerebellar ataxia, as well as in SCA6, but gaze-evoked nystagmus was observed less frequently in 16q-ADCA patients than in SCA6 patients. When compared at almost the same disease duration after onset, the severity of cerebellar ataxia was a little higher, and the progression rate seemed more rapid in 16q-ADCA patients than in SCA6 patients, but the differences were not significant. GLOSSARY ADCA = autosomal dominant cerebellar ataxia, 16q-ADCA = 16q22.1-linked autosomal dominant cerebellar ataxia, SCD = spinocerebellar degeneration, SCA6 = spinocerebellar ataxia type 6, ICARS = international cerebellar ataxia rating scales, SARA = scales for the assessment and rating of ataxia

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A clinical, genetic, and neuropathologic study in a family with 16q-linked ADCA type III

Cited by 69 publications

References 8 publications

Secretory Carrier Membrane Protein 2 Regulates Cell-surface Targeting of Brain-enriched Na+/H+ Exchanger NHE5

Secretory Carrier Membrane Protein 2 Regulates Cell-surface Targeting of Brain-enriched Na+/H+ Exchanger NHE5

Rare frequency of downbeat positioning nystagmus in spinocerebellar ataxia type 31

Severity and Progression Rate of Cerebellar Ataxia in 16q-linked Autosomal Dominant Cerebellar Ataxia (16q-ADCA) in the Endemic Nagano Area of Japan

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