BSMAP, a Novel Protein Expressed Specifically in the Brain Whose Gene Is Localized on Chromosome 19p12

Elson, Greg; Coignac, Amélie Benoit de; Aubry, Jean‐Pierre; Delneste, Yves; Magistrelli, Giovanni; Holzwarth, James A.; Bonnefoy, Jean‐Yves; Gauchat, Jean‐François

doi:10.1006/bbrc.1999.1481

Cited by 12 publications

(10 citation statements)

References 16 publications

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“…The single knockdown of TMEM59 or TMEM59L did not significantly affect APP shedding or maturation (data not shown). This may be due to the fact that even in the absence of one or both proteins, the other homolog is still present, because both proteins are expressed in HEK293 cells (30). In fact, the combined knockdown of TMEM59 and TMEM59L reduced shedding of the endogenous APPs␣ and APPs␤ by 30 -40%, respectively (Fig.…”

Section: Tmem59 Modulates Maturation and Shedding Of App-tomentioning

confidence: 99%

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The Novel Membrane Protein TMEM59 Modulates Complex Glycosylation, Cell Surface Expression, and Secretion of the Amyloid Precursor Protein

Ullrich

Münch

Neumann

et al. 2010

Journal of Biological Chemistry

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Ectodomain shedding of the amyloid precursor protein (APP) by the two proteases ␣-and ␤-secretase is a key regulatory event in the generation of the Alzheimer disease amyloid ␤ peptide (A␤). At present, little is known about the cellular mechanisms that control APP shedding and A␤ generation. Here, we identified a novel protein, transmembrane protein 59 (TMEM59), as a new modulator of APP shedding. TMEM59 was found to be a ubiquitously expressed, Golgi-localized protein. TMEM59 transfection inhibited complex N-and O-glycosylation of APP in cultured cells. Additionally, TMEM59 induced APP retention in the Golgi and inhibited A␤ generation as well as APP cleavage by ␣-and ␤-secretase cleavage, which occur at the plasma membrane and in the endosomes, respectively. Moreover, TMEM59 inhibited the complex N-glycosylation of the prion protein, suggesting a more general modulation of Golgi glycosylation reactions. Importantly, TMEM59 did not affect the secretion of soluble proteins or the ␣-secretase like shedding of tumor necrosis factor ␣, demonstrating that TMEM59 did not disturb the general Golgi function. The phenotype of TMEM59 transfection on APP glycosylation and shedding was similar to the one observed in cells lacking conserved oligomeric Golgi (COG) proteins COG1 and COG2. Both proteins are required for normal localization and activity of Golgi glycosylation enzymes. In summary, this study shows that TMEM59 expression modulates complex N-and O-glycosylation and suggests that TMEM59 affects APP shedding by reducing access of APP to the cellular compartments, where it is normally cleaved by ␣-and ␤-secretase. Processing of the amyloid precursor protein (APP)3 by two different proteases, called ␣-and ␤-secretase, is a central regulatory event in the generation of the amyloid ␤ peptide (A␤), which has a key role in Alzheimer disease (AD) pathogenesis (1). Both ␣-and ␤-secretase cleave the type I membrane protein APP within its ectodomain close to its transmembrane domain (2). This leads to the secretion of soluble forms of APP (APPs) and is referred to as APP shedding. The ␤-secretase is the aspartyl protease BACE1 and cleaves APP at the N terminus of the A␤ peptide domain, thus catalyzing the first step in A␤ peptide generation (3, 4). After the initial cleavage of APP by BACE1, the remaining C-terminal APP fragment is cleaved by ␥-secretase within its transmembrane domain at the C terminus of the A␤ domain, leading to the secretion of the A␤-peptide (5). In contrast to ␤-secretase, ␣-secretase cleaves within the A␤-sequence of APP, and thereby precludes A␤ peptide generation. Additionally, ␣-but not ␤-secretase cleavage generates a secreted form of APP (APPs␣), which has neurotrophic and neuroprotective properties (6 -8). The ␣-secretase is a member of the ADAM family (A disintegrin and metalloprotease) of proteases (9 -12). At present little is known about how the cell controls access of APP to its secretases and the amount of ␣-and ␤-secretase cleavage (reviewed in Refs. 13 and 14). Recent studies increasingl...

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Section: Tmem59 Modulates Maturation and Shedding Of App-tomentioning

confidence: 99%

“…The protein was identified from a human cDNA library, which we screened for modulators of APP shedding (28,29). TMEM59 has a distant homolog called TMEM59L or BSMAP (brain-specific membrane-associated protein), which is expressed in brain, but also in peripheral tissues and in human embryonic kidney 293 cells (30) (sequence alignment shown in Fig. 1).…”

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confidence: 99%

The Novel Membrane Protein TMEM59 Modulates Complex Glycosylation, Cell Surface Expression, and Secretion of the Amyloid Precursor Protein

Ullrich

Münch

Neumann

et al. 2010

Journal of Biological Chemistry

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“…S1I). This protein domain contains many glycosylation sites and is only found in eukaryotes [45]. 10403 transcripts are detected in all vitellocytes in the vitellarium and vitelline duct but not in the ovo-vitelline duct (Fig.…”

Section: Resultsmentioning

confidence: 99%

Transcriptional Analysis of a Unique Set of Genes Involved in Schistosoma mansoni Female Reproductive Biology

Cogswell¹,

Kommer²,

Williams

2012

PLoS Negl Trop Dis

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Schistosomiasis affects more than 200 million people globally. The pathology of schistosome infections is due to chronic tissue inflammation and damage from immune generated granulomas surrounding parasite eggs trapped in host tissues. Schistosoma species are unique among trematode parasites because they are dioecious; females require paring with male parasites in order to attain reproductive maturity and produce viable eggs. Ex vivo cultured females lose the ability to produce viable eggs due to an involution of the vitellarium and loss of mature oocytes. In order to better understand schistosome reproductive biology we used data generated by serial analysis of gene expression (SAGE) to identify uncharacterized genes which have different transcript abundance in mature females, those that have been paired with males, and immature females obtained from unisexual infections. To characterize these genes we used bioinformatics, transcript localization, and transcriptional analysis during the regression of in vitro cultured females. Genes transcribed exclusively in mature females localize primarily in the vitellocytes and/or the ovary. Genes transcribed exclusively in females from single sex infections localize to vitellocytes and subtegumental cells. As female reproductive tissues regress, eggshell precursor proteins and genes involved in eggshell synthesis largely have decreased transcript abundance. However, some genes with elevated transcript abundance in mature adults have increased gene expression following regression indicating that the genes in this study function both in eggshell biology as well as vitellogenesis and maintenance of female reproductive tissues. In addition, we found that genes enriched in females from single sex infections have increased expression during regression in ex vivo females. By using these transcriptional analyses we can direct research to examine the areas of female biology that are both relevant to understanding the overall process of female development and worm pairing while determining novel therapeutic approaches directed at the maturation of female schistosomes.

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“…Tmem59l (transmembrane protein 59‐like) is a single‐pass type I membrane glycoprotein expressed within the Golgi apparatus that has not been functionally examined in branching morphogenesis. First identified in the human brain as BSMAP (brain‐specific membrane‐anchored protein), Tmem59l was suggested to have caspase‐dependent apoptotic activity and modulate amyloid precursor protein shedding . Furthermore, mouse behavioral studies have implicated the downregulation of Tmem59l in reducing depression and anxiety, while increasing memory …”

Section: Introductionmentioning

confidence: 99%

Mutational analysis of genes with ureteric progenitor cell‐specific expression in branching morphogenesis of the mouse kidney

Rutledge

McMahon

2020

Developmental Dynamics

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Background: Ureteric progenitor cells (UPCs) within the branch tips of the arborizing ureteric epithelium of the kidney's developing collecting system establish the shape and cellular organization of the collecting network, and drive the nephrogenic program through their interactions with nephron progenitor cells. In a previous study, expression screening identified a cohort of genes showing UPC-enriched expression including D17H6S56E-5, Hs3st3a1, Hs3st3b1, and Tmem59l. Each of these is also enriched in branch tips of assembling airways of the developing lungs. Here, we used Crispr-CAS9 directed gene editing to mutate each of these targets to address their potential role(s) in UPC programs.Results: Single (D17H6S56E-5 and Tmem59l) and double (Hs3st3a1 and Hs3st3b1) mutants were viable, fertile, and displayed varying frequencies of ureter duplications and no overt lung phenotype. Ureter duplications arise spontaneously through multiple outgrowths of the ureteric bud at the onset of kidney development. Tmem59l mutants and Hs3st3a1/Hs3st3b1 compound mutants showed a weakly penetrant, but statistically significant increase in duplicated ureters compared to C57BL6/J and SW wild-type mouse strains.Conclusions: Tmem59l and Hs3st3a1/Hs3st3b1 activities contribute to the regulatory programs restricting ureteric outgrowth in the developing mouse kidney. However, the low penetrance of the observed phenotype precludes a detailed analysis of their specific actions.

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BSMAP, a Novel Protein Expressed Specifically in the Brain Whose Gene Is Localized on Chromosome 19p12

Cited by 12 publications

References 16 publications

The Novel Membrane Protein TMEM59 Modulates Complex Glycosylation, Cell Surface Expression, and Secretion of the Amyloid Precursor Protein

The Novel Membrane Protein TMEM59 Modulates Complex Glycosylation, Cell Surface Expression, and Secretion of the Amyloid Precursor Protein

Transcriptional Analysis of a Unique Set of Genes Involved in Schistosoma mansoni Female Reproductive Biology

Mutational analysis of genes with ureteric progenitor cell‐specific expression in branching morphogenesis of the mouse kidney

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