Stage-Specific Expression of a Mouse Homologue of the Porcine 135kDa α-D-Mannosidase (MAN2B2) in Type A Spermatogonia

Hiramoto, Shinsuke; Tamba, Michiko; Kiuchi, Sachiko; Jin, Yin‐Zhe; Bannai, Shiro; Sugita, Yoshiki; Dacheux, Françoise; Dacheux, Jean‐Louis; Yoshida, Midori; Okamura, Nobuyuki

doi:10.1006/bbrc.1997.7768

Cited by 17 publications

(15 citation statements)

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“…The low pH optimum and the prior data demonstrating the lysosomal localization for the core-specific ␣1,6-mannosidase (21, 22, 24 -26) indicate that the human ␣1,6-mannosidase characterized here is involved in lysosomal N-glycan catabolism. The absence of any detectable activity toward Man 3 GlcNAc 2 substrates or larger high mannose substrates would likely preclude a role for this enzyme in the modification of spermsurface glycoproteins in the epididymis or testis as originally proposed for the porcine and murine forms of the enzyme (29,31).…”

Section: ϩmentioning

confidence: 99%

“…Noteworthy is the lack of any sequence homologs within this latter clade from D. melanogaster, C. elegans, A. thaliana, or any other nonvertebrate source. The cDNAs encoding the pig and mouse homologs have been cloned previously as the respective epididymal ␣-mannosidases (29,31), but recombinant enzyme expression or characterization has not been accomplished. A sequence alignment of the human, mouse, and pig sequences from this clade is shown in Fig.…”

Section: Isolation Of a Human Cdna Homolog Of The Pig And Mouse 135-kdamentioning

confidence: 99%

“…The enzyme was initially isolated from porcine caudal epididymal fluid, and Northern blots indicated transcript expression restricted to the border of the caput and corpus epididymis (29). Mouse transcripts encoding the enzyme were found exclusively in type A spermatogonia at stages IX-XI of spermatogenesis (31). In contrast, subsequent studies have shown that transcripts encoding the murine ortholog of the ␣1,6-mannosidase are not restricted to reproductive tissues, but they are ubiquitously expressed (32), consistent with our present data demonstrating a ubiquitous expression of transcripts encoding the human enzyme (Fig.…”

Section: ϩmentioning

confidence: 99%

“…Both pig (29) and mouse (31) cDNA homologs encoding this enzyme have been cloned, but no recombinant enzyme expression or detailed substrate specificity data have been presented.…”

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Characterization of a Human Core-specific Lysosomal α1,6-Mannosidase Involved in N-Glycan Catabolism

Park

Stanton

et al. 2005

Journal of Biological Chemistry

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In humans and rodents, the lysosomal catabolism of core Man 3 GlcNAc 2 N-glycan structures is catalyzed by the concerted action of several exoglycosidases, including a broad specificity lysosomal ␣-mannosidase (LysMan), core-specific ␣1,6-mannosidase, ␤-mannosidase, and cleavage at the reducing terminus by a di-Nacetylchitobiase. We describe here the first cloning, expression, purification, and characterization of a novel human glycosylhydrolase family 38 ␣-mannosidase with catalytic characteristics similar to those established previously for the core-specific ␣1,6-mannosidase (acidic pH optimum, inhibition by swainsonine and 1,4-dideoxy-1,4-imino-D-mannitol, and stimulation by Co 2؉ and Zn 2؉). Substrate specificity studies comparing the novel human ␣-mannosidase with human LysMan revealed that the former enzyme efficiently cleaved only the ␣1-6mannose residue from Man 3 GlcNAc but not Man 3 GlcNAc 2 or other larger high mannose oligosaccharides, indicating a requirement for chitobiase action before ␣1,6-mannosidase activity. In contrast, LysMan cleaved all of the ␣-linked mannose residues from high mannose oligosaccharides except the core ␣1-6mannose residue. ␣1,6-Mannosidase transcripts were ubiquitously expressed in human tissues, and expressed sequence tag searches identified homologous sequences in murine, porcine, and canine databases. No expressed sequence tags were identified for bovine ␣1,6-mannosidase, despite the identification of two sequence homologs in the bovine genome. The lack of conservation in 5-flanking sequences for the bovine ␣1,6-mannosidase genes may lead to defective transcription similar to transcription defects in the bovine chitobiase gene. These results suggest that the chitobiase and ␣1,6-mannosidase function in tandem for mammalian lysosomal N-glycan catabolism.

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Section: ϩmentioning

confidence: 99%

Section: Isolation Of a Human Cdna Homolog Of The Pig And Mouse 135-kdamentioning

confidence: 99%

Section: ϩmentioning

confidence: 99%

“…Both pig (29) and mouse (31) cDNA homologs encoding this enzyme have been cloned, but no recombinant enzyme expression or detailed substrate specificity data have been presented.…”

mentioning

confidence: 99%

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Characterization of a Human Core-specific Lysosomal α1,6-Mannosidase Involved in N-Glycan Catabolism

Park

Stanton

et al. 2005

Journal of Biological Chemistry

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“…The gene encoding epididymis-specific ␣-D-mannosidase (Man2b2; GenBank accession no. U29947), 30 an unlikely candidate, was the only known gene within the interval. We screened the remaining candidates by a combination of Northern blot analysis, Southern blot analysis of gDNA digested with multiple restriction enzymes, and direct sequencing.…”

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confidence: 99%

Cappuccino, a mouse model of Hermansky-Pudlak syndrome, encodes a novel protein that is part of the pallidin-muted complex (BLOC-1)

Ciciotte

Gwynn

Moriyama

et al. 2003

Blood

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Hermansky-Pudlak syndrome (HPS) is a disorder of organelle biogenesis affecting 3 related organelles-melanosomes, platelet dense bodies, and lysosomes. Four genes causing HPS in humans (HPS1-HPS4) are known, and at least 15 nonallelic mutations cause HPS in the mouse. Where their functions are known, the HPS-associated proteins are involved in some aspect of intracellular vesicular trafficking, that is, protein sorting and vesicle docking and fusion. Biochemical and genetic evidence indicates that the HPS-associated genes encode components of at least 3 distinct protein complexes: the adaptor complex AP-3; the HPS1/HPS4 complex; and BLOC-1 (biogenesis of lysosome-related organelles complex-1), consisting of the proteins encoded at 2 mouse HPS loci, pallid (pa) and muted (mu), and at least 3 other unidentified proteins. Here, we report the cloning of the mouse HPS mutation cappuccino (cno). We show that the wild-type cno gene encodes a novel, ubiquitously expressed cytoplasmic protein that coassembles with pallidin and the muted protein in the BLOC-1 complex. Further, we identify a frameshift mutation in mutant cno/cno mice. The C-terminal 81 amino acids are replaced with 72 different amino acids in the mutant CNO protein, and its ability to interact in BLOC-1 is abolished. We performed mutation screening of patients with HPS and failed to identify any CNO defects. Notably, although defects in components of the HPS1/HPS4 and the AP-3 complexes are associated with HPS in humans, no defects in the known components of BLOC-1 have been identified in 142 patients with HPS screened to date, suggesting that BLOC-1 function may be critical in humans. IntroductionIn the autosomal recessive Hermansky-Pudlak syndrome (HPS) defects in lysosome-related organelles (melanosomes, platelet dense bodies, lysosomes) cause albinism, prolonged bleeding, and lysosomal storage disease. 1,2 The worldwide incidence of HPS is unknown, but it occurs in all ethnic groups and its frequency is very high in some populations due to founder effects (eg, Northwest Puerto Rico, 1/1800). 3 HPS is associated with considerable morbidity and mortality. Melanosome defects lead to oculocutaneous albinism resulting in nystagmus, decreased visual acuity, and skin damage on exposure to sunlight. 4 Platelet dense body defects result in prolonged bleeding, which can be severe. 4,5 Pulmonary fibrotic disease, possibly the result of ceroid lipofuscin accumulation in lysosomes, is progressive and is known to occur in patients with HPS-1 and HPS-4. In such individuals, death typically occurs in the fourth to fifth decades. [5][6][7] In mice, at least 15 nonallelic mutations cause HPS. 8 Eight are cloned, including the orthologues of the human genes HPS1-HPS4 (pale ear [ep], pearl [pe], cocoa [coa], light ear [le]), and mocha (mh), pallid (pa), ashen (ash), and muted (mu). [9][10][11][12][13][14][15][16][17] The known or suspected functions of the HPS proteins implicate them in some aspect of intracellular vesicular trafficking in the biogenesis of lysosome-rel...

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Proteomic analysis of human lysosomes: Application to monocytic and breast cancer cells

et al. 2002

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To date, about fifty lysosomal hydrolases have been identified, and most of them are targeted towards the lysosomes through a specific mannose-6-phosphate (M-6-P) tag. As more lysosomal hydrolases were expected to be discovered, we performed a proteomic study of soluble lysosomal proteins. Human cells were induced to secrete M-6-P proteins which were affinity purified on immobilized M-6-P receptor. The purified proteins were resolved by two-dimensional electrophoresis and analyzed by mass spectrometry. Twenty-two proteins were identified, among which 16 were well-known lysosomal hydrolases. The remaining species distributed as follows: epididymis-specific alpha-mannosidase is a new mannosidase homolog, cystatin F and CREG (cellular repressor of E1A-stimulated genes) were previously identified as M-6-P proteins (Journet et al., Electrophoresis 2000, 21, 3411-3419), and the last three, which are not hydrolases, were up to now considered as nonlysosomal. This two-dimensional reference map of human U937 M-6-P proteins was afterwards used for comparison with M-6-P proteins purified either from U937 differentiated into macrophage-like cells, or from human breast cancer MCF7 cells. Phorbol ester induced differentiation of U937 cells led to limited proteolytic cleavage or maturation of a discrete number of hydrolases. Five additional lysosomal hydrolases were identified from MCF7 samples. These results prove the usefulness of such a procedure to analyze the lysosomal content of various cell lines, to discover new M-6-P proteins, as well as to point towards unknown biological processes.

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Stage-Specific Expression of a Mouse Homologue of the Porcine 135kDa α-D-Mannosidase (MAN2B2) in Type A Spermatogonia

Cited by 17 publications

References 0 publications

Characterization of a Human Core-specific Lysosomal α1,6-Mannosidase Involved in N-Glycan Catabolism

Characterization of a Human Core-specific Lysosomal α1,6-Mannosidase Involved in N-Glycan Catabolism

Cappuccino, a mouse model of Hermansky-Pudlak syndrome, encodes a novel protein that is part of the pallidin-muted complex (BLOC-1)

Proteomic analysis of human lysosomes: Application to monocytic and breast cancer cells

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