A novel membrane protein, encoded by the gene covering KIAA0233, is transcriptionally induced in senile plaque-associated astrocytes

Satoh, Kaneo; Hata, Mieko; Takahara, Seiji; Tsuzaki, Hidetoshi; Yokota, Hiroshi; Akatsu, Hiroyasu; Yamamoto, Takayuki; Kosaka, Kenji; Yamada, Tatsuo

doi:10.1016/j.brainres.2006.06.050

Cited by 61 publications

(61 citation statements)

References 20 publications

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“…In transiently transfected CHO-K1 cells, Fam38A localisation was consistent with observations of the rat homologue to Fam38A, Mib, which was shown to be at the ER (Satoh et al, 2006) (Fig. 5A).…”

Section: Fam38a Localises To the Ersupporting

confidence: 87%

“…2A. KIAA0233 has been described as the human orthologue of the rat gene Mib, which is upregulated in senile-plaque-associated astrocytes (Satoh et al, 2006), and codes for a large (2090 amino acids, >230 kDa) novel membrane protein identified as Fam38A in GenBank. Fam38A contains an N-terminal signal sequence and 24 transmembrane domains, suggesting that it might form a membranous pore or channel, and is conserved throughout multicellular eukaryotes.…”

Section: Identification Of Fam38a From a Screen For Reversal Of H-rasmentioning

confidence: 99%

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Integrin activation by Fam38A uses a novel mechanism of R-Ras targeting to the endoplasmic reticulum

McHugh

Buttery

Lad

et al. 2010

Journal of Cell Science

180

173

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SummaryThe integrin family of heterodimeric cell-surface receptors are fundamental in cell-cell and cell-matrix adhesion. Changes to either integrin-ligand affinity or integrin gene expression are central to a variety of disease processes, including inflammation, cardiovascular disease and cancer. In screening for novel activators of integrin-ligand affinity we identified the previously uncharacterised multitransmembrane domain protein Fam38A, located at the endoplasmic reticulum (ER). siRNA knockdown of Fam38A in epithelial cells inactivates endogenous b1 integrin, reducing cell adhesion. Fam38A mediates integrin activation by recruiting the small GTPase RRas to the ER, which activates the calcium-activated protease calpain by increasing Ca 2+ release from cytoplasmic stores. Fam38A-induced integrin activation is blocked by inhibition of either R-Ras or calpain activity, or by siRNA knockdown of talin, a welldescribed calpain substrate. This highlights a novel mechanism for integrin activation by Fam38A, utilising calpain and R-Ras signalling from the ER. These data represent the first description of a novel spatial regulator of R-Ras, of an alternative integrin activationsuppression pathway based on direct relocalisation of R-Ras to the ER, and of a mechanism linking R-Ras and calpain signalling from the ER with modulation of integrin-ligand affinity.

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Section: Fam38a Localises To the Ersupporting

confidence: 87%

Section: Identification Of Fam38a From a Screen For Reversal Of H-rasmentioning

confidence: 99%

Integrin activation by Fam38A uses a novel mechanism of R-Ras targeting to the endoplasmic reticulum

McHugh

Buttery

Lad

et al. 2010

Journal of Cell Science

180

173

View full text Add to dashboard Cite

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“…46 Both variants were found in pedigree five, and are considered probably damaging, with PolyPhen2 47 scores of 0.997 (rs202103485) and 0.999 (rs200970763). The variants in histidine rich carboxyl terminus 1 ( HRCT1 ), found in pedigree 5, and in transmembrane protein 141 ( TMEM141 ), found in pedigree 12, were rare in all comparison data sets.…”

Section: Discussionmentioning

confidence: 99%

Genetic risk factors in two Utah pedigrees at high risk for suicide

et al. 2013

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We have used unique population-based data resources to identify 22 high-risk extended pedigrees that show clustering of suicide over twice that expected from demographically adjusted incidence rates. In this initial study of genetic risk factors, we focused on two high-risk pedigrees. In the first of these (pedigree 12), 10/19 (53%) of the related suicides were female, and the average age at death was 30.95. In the second (pedigree 5), 7/51 (14%) of the suicides were female and the average age at death was 36.90. Six decedents in pedigree 12 and nine in pedigree 5 were genotyped with the Illumina HumanExome BeadChip. Genotypes were analyzed using the Variant Annotation, Analysis, and Search program package that computes likelihoods of risk variants using the functional impact of the DNA variation, aggregative scoring of multiple variants across each gene and pedigree structure. We prioritized variants that were: (1) shared across pedigree members, (2) rare in other Utah suicides not related to these pedigrees, (3) ⩽ 5% in genotyping data from 398 other Utah population controls and (4) ⩽5% frequency in publicly available sequence data from 1358 controls and/or in dbSNP. Results included several membrane protein genes (ANO5, and TMEM141 for pedigree 12 and FAM38A and HRCT1 for pedigree 5). Other genes with known neuronal involvement and/or previous associations with psychiatric conditions were also identified, including NFKB1, CASP9, PLXNB1 and PDE11A in pedigree 12, and THOC1, and AUTS2 in pedigree 5. Although the study is limited to variants included on the HumanExome BeadChip, these findings warrant further exploration, and demonstrate the utility of this high-risk pedigree resource to identify potential genes or gene pathways for future development of targeted interventions.

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“…Its expression is induced in senile plaque-associated astrocytes (14), and the protein has been suggested to be involved in integrin activation (15). Extracellular perfusion of cells with buffer lacking divalent ions and containing 5 mM EGTA for 30-60 min, which disrupts integrin function (16), did not suppress MA currents (Fig.…”

Section: Piezo1 (Fam38a) Is Required For Ma Currents Of N2a Cellsmentioning

confidence: 99%

Piezo1 and Piezo2 Are Essential Components of Distinct Mechanically Activated Cation Channels

Coste

Mathur

Schmidt

et al. 2010

Science

2,417

133

2,862

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Mechanical stimuli drive many physiological processes, including touch and pain sensation, hearing, and blood pressure regulation. Mechanically-activated (MA) cation channel activities have been recorded in many cells, but the responsible molecules have not been identified. We characterized a rapidly-adapting MA current in a mouse neuroblastoma cell line. Expression profiling and RNAi knockdown of candidate genes identified Piezo1 (Fam38A) to be required for MA currents in these cells. Piezo1 and related Piezo2 (Fam38B) are vertebrate multipass transmembrane proteins with homologs in invertebrates, plants, and protozoa. Overexpression of mouse Piezo1 or Piezo2 induced two kinetically-distinct MA currents. Piezos are expressed in several tissues, and knockdown of Piezo2 in dorsal root ganglia neurons specifically reduced rapidly-adapting MA currents. We propose that Piezos are components of mechanically-activated cation channels.

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A novel membrane protein, encoded by the gene covering KIAA0233, is transcriptionally induced in senile plaque-associated astrocytes

Cited by 61 publications

References 20 publications

Integrin activation by Fam38A uses a novel mechanism of R-Ras targeting to the endoplasmic reticulum

Integrin activation by Fam38A uses a novel mechanism of R-Ras targeting to the endoplasmic reticulum

Genetic risk factors in two Utah pedigrees at high risk for suicide

Piezo1 and Piezo2 Are Essential Components of Distinct Mechanically Activated Cation Channels

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