4.8 Article

Lack of the endosomal SNAREs vti1a and vti1b led to significant impairments in neuronal development

出版社

NATL ACAD SCIENCES
DOI: 10.1073/pnas.1013891108

关键词

endosome; neurite outgrowth; neuronal survival

资金

  1. Deutsche Forschungsgemeinschaft (DFG) [FI583/4-1, Kr1477/11-3, SFB780-B02, SFB523-B16]

向作者/读者索取更多资源

Fusion between membranes is mediated by specific SNARE complexes. Here we report that fibroblasts survive the absence of the trans-Golgi network/early endosomal SNARE vti1a and the late endosomal SNARE vti1b with intact organelle morphology and minor trafficking defects. Because vti1a and vti1b are the only members of their SNARE subclass and the yeast homolog Vti1p is essential for cell survival, these data suggest that more distantly related SNAREs acquired the ability to function in endosomal traffic during evolution. However, absence of vti1a and vti1b resulted in perinatal lethality. Major axon tracts were missing, reduced in size, or misrouted in Vti1a(-/-) Vti1b(-/-) embryos. Progressive neurodegeneration was observed in most Vti1a(-/-) Vti1b(-/-) peripheral ganglia. Neurons were reduced by more than 95% in Vti1a(-/-) Vti1b(-/-) dorsal root and geniculate ganglia at embryonic day 18.5. These data suggest that special demands for endosomal membrane traffic could not be met in Vti1a(-/-) Vti1b(-/-) neurons. Vti1a(-/-) and Vti1b(-/-) single deficient mice were viable without these neuronal defects, indicating that they can substitute for each other in these processes.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.8
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

Article Genetics & Heredity

Genetic analysis of children with congenital ocular anomalies in three ecological regions of Nepal: a phase II of Nepal pediatric ocular diseases study

Srijana Adhikari, Neelam Thakur, Ujjowala Shrestha, Mohan K. Shrestha, Murarai Manshrestha, Bijay Thapa, Manish Poudel, Ajaya Kunwar

BMC MEDICAL GENETICS (2020)

Article Chemistry, Inorganic & Nuclear

Stronger Cytotoxicity for Cancer Cells Than for Fast Proliferating Human Stem Cells by Rationally Designed Dinuclear Complexes

Sabrina Schwarzbich, Claudia Horstmann nee Gruschka, Jasmin Simon, Lena Siebe, Alexander Moreth, Christiane Wiegand, Antonina Lavrentieva, Thomas Scheper, Anja Stammler, Hartmut Boegge, Gabriele Fischer von Mollard, Thorsten Glaser

INORGANIC CHEMISTRY (2020)

Article Microbiology

Recombinant expression of anl-amino acid oxidase from the fungusHebeloma cylindrosporuminPichia pastorisincluding fermentation

Marc Christian Hess, Svenja Bloess, Joe Max Risse, Karl Friehs, Gabriele Fischer von Mollard

MICROBIOLOGYOPEN (2020)

Article Neurosciences

Ablation of Vti1a/1b Triggers Neural Progenitor Pool Depletion and Cortical Layer 5 Malformation in Late-embryonic Mouse Cortex

Godwin Sokpor, Joachim Rosenbusch, Ajaya J. Kunwar, Michael Rickmann, Tran Tuoc, Silvio O. Rizzoli, Victor Tarabykin, Gabriele Fischer von Mollard, Kerstin Krieglstein, Jochen F. Staiger

Summary: Vti1a/1b play key roles in regulating neuronal growth and are essential for proper cortical development. Deletion of Vti1a/1b results in cortical dysgenesis in mice, particularly affecting the organization of cortical layer 5 and leading to neuronal apoptosis.

NEUROSCIENCE (2021)

Article Microbiology

Analysis of N-glycosylation in fungal l-amino acid oxidases expressed in the methylotrophic yeast Pichia pastoris

Marc Christian Hess, Marvin Grollius, Valentin Duhay, Simon Koopmeiners, Svenja Bloess, Gabriele Fischer von Mollard

Summary: The study demonstrated the heterologous expression of four fungal LAAOs in Pichia pastoris, showing that the enzymatic activity of some enzymes for substrate conversion is influenced by N-glycosylation, with one enzyme's activity depending on specific N-glycosylation modification.

MICROBIOLOGYOPEN (2021)

Article Chemistry, Physical

Efficient Site-Selective Immobilization of Aldehyde-Tagged Peptides and Proteins by Knoevenagel Ligation

Nils Janson, Tobias Heinks, Tobias Beuel, Sarfaraz Alam, Matthias Hoehne, Uwe T. Bornscheuer, Gabriele Fischer von Mollard, Norbert Sewald

Summary: The aldehyde tag is used for selective labeling of proteins and preparing antibody-drug conjugates, or immobilizing enzymes or antibodies. A new solid support, modified agarose with an aryl substituted pyrazolone, allows site-selective and efficient immobilization of aldehyde-containing molecules under physiological pH without the need for additives or catalysts. Compared to reductive amination, the modified agarose achieves higher loadings and activities in various buffers at different concentrations and temperatures.

CHEMCATCHEM (2022)

Article Biochemistry & Molecular Biology

Recombinant l-Amino Acid Oxidase with Broad Substrate Spectrum for Co-substrate Recycling in (S)-Selective Transaminase-Catalyzed Kinetic Resolutions

Tobias Heinks, Jannik Paulus, Simon Koopmeiners, Tobias Beuel, Norbert Sewald, Matthias Hoehne, Uwe T. Bornscheuer, Gabriele Fischer von Mollard

Summary: Chiral and enantiopure amines can be synthesized through a dual-enzyme recycling system, which reduces the amount of transaminase co-substrate and alpha-keto acids by utilizing heterologously produced fungal hcLAAO4 and catalase. This system enables the kinetic resolution of racemic amines.

CHEMBIOCHEM (2022)

Review Cell Biology

A Review on Recent Advances of Cerebral Palsy

Sudip Paul, Anjuman Nahar, Mrinalini Bhagawati, Ajaya Jang Kunwar

Summary: This review summarizes the latest advances in cerebral palsy, including prevalence, risk factors, classification, diagnosis methods, and treatment strategies. It also analyzes the technological advancements in prevention, diagnosis, and treatment.

OXIDATIVE MEDICINE AND CELLULAR LONGEVITY (2022)

Article Cell Biology

The SNARE protein Vti1b is recruited to the sites of BCR activation but is redundant for antigen internalisation, processing and presentation

Amna Music, Blanca Tejeda-Gonzalez, Diogo M. Cunha, Gabriele Fischer von Mollard, Sara Hernandez-Perez, Pieta K. Mattila

Summary: This study investigated the localization and function of SNARE protein Vti1b in B lymphocytes. The results showed that Vti1b was localized at the Golgi complex, MTOC, and lysosomal vesicles, and it was partially localized to internalized antigen vesicles and immunological synapse upon BCR activation. However, the absence of Vti1b in B cells did not affect BCR signaling, immunological synapse formation, or processing and presentation of internalized antigen.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2022)

Article Developmental Biology

Primary neurons lacking the SNAREs vti1a and vti1b show altered neuronal development

Christian Bollmann, Susanne Schoening, Katharina Kotschnew, Julia Grosse, Nicole Heitzig, Gabriele Fischer von Mollard

Summary: This study reveals the importance of vti1a and vti1b in neuronal growth and confirms their interaction with other SNARE proteins. Loss of vti1a and vti1b leads to neuronal developmental defects and neurodegeneration.

NEURAL DEVELOPMENT (2022)

Article Chemistry, Physical

Comparison of Four Immobilization Methods for Different Transaminases

Tobias Heinks, Nicolai Montua, Michelle Teune, Jan Liedtke, Matthias Hoehne, Uwe T. Bornscheuer, Gabriele Fischer von Mollard

Summary: This study aims to compare the stability of soluble and immobilized transaminases from different species. Immobilization of transaminases enabled their reusability for at least 10 cycles and maintained full or high activity. Upscaled kinetic resolutions demonstrated high conversion, maintained enantioselectivity, and high product yields, showing their applicability.

CATALYSTS (2023)

Article Chemistry, Physical

Biosynthesis of Furfurylamines in Batch and Continuous Flow by Immobilized Amine Transaminases

Tobias Heinks, Luisa M. Merz, Jan Liedtke, Matthias Hoehne, Luuk M. van Langen, Uwe T. Bornscheuer, Gabriele Fischer von Mollard, Per Berglund

Summary: In this study, four different amine transaminases (ATAs) were identified to catalyze the reductive amination of 5-(hydroxymethyl)furfural (HMF) and 2,5-diformylfuran (DFF). These ATAs were successfully immobilized on glutaraldehyde-functionalized amine beads and on amine beads by site-selective binding. Immobilized ATAs showed efficient reuse in the reductive amination of HMF with alanine as co-substrate, and the ATA-Spo exhibited high stability for reuse when isopropylamine was used as an amine donor. Additionally, immobilized ATA-Spo achieved high conversion in batch syntheses and continuous-flow catalysis using alanine or isopropylamine as amine donors.

CATALYSTS (2023)

Article Biochemistry & Molecular Biology

Co-Immobilization of a Multi-Enzyme Cascade: (S)-Selective Amine Transaminases, l-Amino Acid Oxidase and Catalase

Tobias Heinks, Simon Koopmeiners, Nicolai Montua, Norbert Sewald, Matthias Hoehne, Uwe T. Bornscheuer, Gabriele Fischer von Mollard

Summary: An enzyme cascade consisting of l-amino acid oxidase (hcLAAO4) and catalase (hCAT) was immobilized together with the (S)-selective amine transaminase (ATA-Vfl) to achieve higher reaction rates and more efficient H2O2-removal. The co-immobilized enzyme cascade showed good stability and high enantiomeric purity in preparative kinetic resolutions. However, further recycling was limited due to the instability of ATA-Vfl. The use of an engineered ATA-Vfl-8M in the immobilized enzyme cascade allowed a significant reduction in the amount of co-substrate required.

CHEMBIOCHEM (2023)

Article Cell Biology

Distinct functional domains of the epsin-related Ent5p, a cargo adaptor for the SNARE Tlg2p in transport between endosomes and Golgi

Lara Petersen, Rimma Bachmann, Sven Meinerz, Anne Tanz, Gabriele Fischer von Mollard

Summary: The epsin-related adaptor proteins Ent3p and Ent5p are involved in the formation of clathrin-coated vesicles during transport between trans-Golgi network and endosomes in yeast. They play different roles in transport, with Ent3p involved in the accumulation of Can1p-GFP in endosomes and Ent5p facilitating faster transport of Can1p-GFP to the vacuole for degradation. The C-terminal domain of Ent5p is sufficient to restore recycling of the secretory SNARE GFP-Snc1p between plasma membrane and TGN in cells with increased Ent3p and Ent5p levels. The interaction between Ent5p's ENTH domain and the SNARE Tlg2p is responsible for transport from early endosomes to the trans-Golgi network. The importance of Ent3p and Ent5p as cargo adaptors for distinct SNAREs is demonstrated.

TRAFFIC (2023)

暂无数据