Judith Blanz

Judith Blanz
Christian-Albrechts-Universität zu Kiel | CAU · Institute of Biochemistry

phd

About

33
Publications
6,602
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3,269
Citations
Citations since 2016
5 Research Items
1842 Citations
2016201720182019202020212022050100150200250300
2016201720182019202020212022050100150200250300
2016201720182019202020212022050100150200250300
2016201720182019202020212022050100150200250300

Publications

Publications (33)
Article
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Significance Extracellular tissue debris accumulates with aging and in the most prevalent central-vision-threatening eye disorder, age-related macular degeneration (AMD). In this work, we discovered that lysosome-associated membrane protein-2 (LAMP2), a glycoprotein that plays a critical role in lysosomal biogenesis and maturation of autophagosomes...
Article
Human-derived neurons provide the answers Pathways involved in energy metabolism and removal of cellular debris by lysosomes play an important role in protecting our brain from degeneration in Parkinson's disease. Burbulla et al. identified a toxic cascade of mitochondrial and lysosomal dysfunction in human neurons derived from patients with Parkin...
Article
Full-text available
Alpha-mannosidosis is a glycoproteinosis caused by deficiency of lysosomal acid alpha-mannosidase (LAMAN), which markedly affects neurons of the central nervous system (CNS), and causes pathognomonic intellectual dysfunction in the clinical condition. Cognitive improvement consequently remains a major therapeutic objective in research on this devas...
Article
Significance Apart from the lysosomal integral membrane protein type-2 (LIMP-2)–dependent trafficking of β-glucocerebrosidase (GC) to lysosomes, little is known about the interaction of LIMP-2 and GC on the molecular level. The structural and biochemical characterization of LIMP-2/GC interaction sites has potential importance for the design of GC-a...
Article
The role of mutations in the gene GBA1 encoding the lysosomal hydrolase β-glucocerebrosidase for the development of synucleinopathies, such as Parkinson's disease and dementia with Lewy bodies, was only very recently uncovered. The knowledge obtained from the study of carriers or patients suffering from Gaucher disease (a common lysosomal storage d...
Data
Figure S4. Long‐term high‐dose ERT efficiently reduces oligosaccharide storage in the brain of mice with established neuropathology. (A) The specific activity of α‐glucuronidase and β‐hexosaminidase show a normalization to control (+/‐) levels after rhLAMAN treatment with 500 U/kg (n = 4–6, per genotype). (B) TLC analysis of oligosaccharide brain e...
Data
Figure S2. Immune‐tolerant alpha‐mannosidase knockout mice are phenotypically indistinguishable from nontransgenic animals. (A) Separation of neutral oligosaccharides extracted from spleens of 3–4 months old wild‐type (+/+), nontransgenic (‐/‐) and transgenic (‐/‐ +tg) mice by thin layer chromatography (TLC) shows comparable amounts of all glycan s...
Data
Figure S3. Long‐term high‐dose ERT efficiently reduces oligosaccharide storage within peripheral tissues. (A) TLC analysis and (B) HPLC of oligosaccharides extracted from kidney of wild‐type (+/+) and both knockout strains shows complete clearance of all major oligosaccharide species in ‐/‐ +tg mice after ERT with both indicated doses. Similar resu...
Data
Figure S1. Development of rhLAMAN‐specific IgG in alpha‐mannosidase knockout mice and generation of immune‐tolerant alpha‐mannosidosis mice. (A) Conventional nontransgenic alpha‐mannosidase knockout mice (‐/‐) develop significant antibody responses after the second injection of recombinant rhLAMAN as determined by ELISA measuring LAMAN‐specific IgG...
Article
Full-text available
Objective The lysosomal storage disease alpha-mannosidosis is caused by the deficiency of the lysosomal acid hydrolase alpha-mannosidase (LAMAN) leading to lysosomal accumulation of neutral mannose-linked oligosaccharides throughout the body, including the brain. Clinical findings in alpha-mannosidosis include skeletal malformations, intellectual d...
Article
The lysosomal integral membrane protein type 2 (LIMP-2/SCARB2) has been described as a mannose 6-phosphate- (M6P) independent trafficking receptor for β-glucocerebrosidase. Recently, a putative M6P residue in a crystal structure of a recombinantely expressed LIMP-2 ectodomain has been reported. Based on surface plasmon resonance and fluorescence li...
Article
Full-text available
Background & aims: The pathogenic mechanism of pancreatitis is poorly understood. Recent evidence implicates defective autophagy in pancreatitis responses; however, the pathways mediating impaired autophagy in pancreas remain largely unknown. Here, we investigate the role of lysosome associated membrane proteins (LAMPs) in pancreatitis. Methods:...
Article
Full-text available
The Lysosomal Associated Membrane Protein type-2 (LAMP-2) is an abundant lysosomal membrane protein with an important role in immunity, macroautophagy (MA) and chaperone-mediated autophagy (CMA). Mutations within the Lamp2 gene cause Danon disease, an X-linked lysosomal storage disorder characterized by (cardio)myopathy and intellectual dysfunction...
Article
Full-text available
Significance Our report highlights, for the first time to our knowledge, a distinct relationship between lysosomal integral membrane protein type-2 (LIMP-2) expression, β-glucocerebrosidase (GC) activity, and clearance of α-synuclein. In LIMP-2–deficient mice, increased levels of endogenous α-synuclein led to severe neurological deficits and premat...
Article
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Background: Alpha-mannosidosis (OMIM 248500) is a rare lysosomal storage disease (LSD) caused by alpha-mannosidase deficiency. Manifestations include intellectual disabilities, facial characteristics and hearing impairment. A recombinant human alpha-mannosidase (rhLAMAN) has been developed for weekly intravenous enzyme replacement therapy (ERT). W...
Article
The lysosomal membrane protein type 2 is a novel identified lysosomal sorting receptor for β-glucocerebrosidase (GC). Mutations in both genes underlie human pathologies causing action myoclonus-renal failure syndrome (AMRF) and Gaucher disease (GD), respectively. We now demonstrate that the lumenal acidification mediated by the vacuolar (H(+) )-ATP...
Article
α-Mannosidosis is a rare lysosomal storage disease with accumulation of undegraded mannosyl-linked oligosaccharides in cells throughout the body, most notably in the CNS. This leads to a broad spectrum of neurological manifestations, including progressive intellectual impairment, disturbed motor functions, and cerebellar atrophy. To develop therape...
Article
Full-text available
Whereas we have a profound understanding about the function and biogenesis of the protein constituents in the lumen of the lysosomal compartment, much less is known about the functions of proteins of the lysosomal membrane. Proteomic analyses of the lysosomal membrane suggest that, apart from the well-known lysosomal membrane proteins, additional a...
Article
The mechanisms of endosomal and lysosomal cholesterol traffic are still poorly understood. We showed previously that unesterified cholesterol accumulates in the late endosomes and lysosomes of fibroblasts deficient in both lysosome associated membrane protein-2 (LAMP-2) and LAMP-1, two abundant membrane proteins of late endosomes and lysosomes. In...
Article
Full-text available
Action myoclonus-renal failure syndrome (AMRF) is caused by mutations in the lysosomal integral membrane protein type 2 (LIMP-2/SCARB2). LIMP-2 was identified as a sorting receptor for β-glucocerebrosidase (β-GC), which is defective in Gaucher disease. To date, six AMRF-causing mutations have been described, including splice site, missense and nons...
Article
Full-text available
Despite the progress in the treatment of lysosomal storage disorders (LSDs) mainly by enzyme replacement therapy, only limited success was reported in targeting the appropriate lysosomal enzyme into the brain. This prevents efficient clearance of neuronal storage, which is present in many of these disorders including alpha-mannosidosis. Here we sho...
Article
Full-text available
Action myoclonus-renal failure syndrome (AMRF) is an autosomal-recessive disorder with the remarkable combination of focal glomerulosclerosis, frequently with glomerular collapse, and progressive myoclonus epilepsy associated with storage material in the brain. Here, we employed a novel combination of molecular strategies to find the responsible ge...
Article
beta-glucocerebrosidase, the enzyme defective in Gaucher disease, is targeted to the lysosome independently of the mannose-6-phosphate receptor. Affinity-chromatography experiments revealed that the lysosomal integral membrane protein LIMP-2 is a specific binding partner of beta-glucocerebrosidase. This interaction involves a coiled-coil domain wit...
Article
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ClC-2 is a broadly expressed plasma membrane chloride channel that is modulated by voltage, cell swelling, and pH. A human mutation leading to a heterozygous loss of ClC-2 has previously been reported to be associated with epilepsy, whereas the disruption of Clcn2 in mice led to testicular and retinal degeneration. We now show that the white matter...
Article
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The ability of KCNQ (Kv7) channels to form hetero-oligomers is of high physiological importance, because heteromers of KCNQ3 with KCNQ2 or KCNQ5 underlie the neuronal M-current, which modulates neuronal excitability. In KCNQ channels, we recently identified a C-terminal subunit interaction (si) domain that determines their subunit-specific assembly...
Article
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In LAMP-2-deficient mice autophagic vacuoles accumulate in many tissues, including liver, pancreas, muscle, and heart. Here we extend the phenotype analysis using cultured hepatocytes. In LAMP-2-deficient hepatocytes the half-life of both early and late autophagic vacuoles was prolonged as evaluated by quantitative electron microscopy. However, an...
Article
Full-text available
Lysosome-associated membrane protein-2 (LAMP-2) is a highly glycosylated protein and an important constituent of the lysosomal membrane. Here we show that LAMP-2 deficiency in mice increases mortality between 20 and 40 days of age. The surviving mice are fertile and have an almost normal life span. Ultrastructurally, there is extensive accumulation...

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