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Your search keyword '"rab GTP-Binding Proteins/genetics"' showing total 2 results
Start Over Descriptor "rab GTP-Binding Proteins/genetics" Topic gene expression regulation
2 results on '"rab GTP-Binding Proteins/genetics"'

1. Increased dosage of RAB39B affects neuronal development and could explain the cognitive impairment in male patients with distal Xq28 copy number gains

Author

Katrin Õunap, Maila Giannandrea, Vigneron Jacqueline, Martine Raynaud, Nathalie Fieremans, Patrizia D'Adamo, Jelle Verbeeck, Hilde Van Esch, Guy Froyen, Lieselot Vanmarsenille, Annick Vogels, Stefanie Belet, Katrin Männik, Sylvain Briault, Clinical sciences, and Medical Genetics

Subjects
Estonia, Male, mice, DNA Copy Number Variations, Methyl-CpG-Binding Protein 2, European Continental Ancestry Group, Non-allelic homologous recombination, Methyl-CpG-Binding Protein 2/genetics, Biology, Hippocampal formation, Bioinformatics, White People, X-inactivation, MECP2, Neurons/cytology, Chromosomes, Human, X/genetics, Belgium, Intellectual Disability, Gene Duplication, rab GTP-Binding Proteins/genetics, Gene duplication, Genetics, Animals, Humans, Child, Gene, Genetics (clinical), Neurons, Regulation of gene expression, Chromosomes, Human, X, Chromosome Mapping, Cell Differentiation, Intellectual Disability/genetics, Xq28, Gene Expression Regulation, rab GTP-Binding Proteins, X chromosome inactivation
Abstract

Copy number gains at Xq28 are a frequent cause of X-linked intellectual disability (XLID). Here, we report on a recurrent 0.5 Mb tandem copy number gain at distal Xq28 not including MECP2, in four male patients with nonsyndromic mild ID and behavioral problems. The genomic region is duplicated in two families and triplicated in a third reflected by more distinctive clinical features. The X-inactivation patterns in carrier females correspond well with their clinical symptoms. Our mapping data confirm that this recurrent gain is likely mediated by nonallelic homologous recombination between two directly oriented Int22h repeats. The affected region harbors eight genes of which RAB39B encoding a small GTPase, was the prime candidate since loss-of-function mutations had been linked to ID. RAB39B is expressed at stable levels in lymphocytes from control individuals, suggesting a tight regulation. mRNA levels in our patients were almost two-fold increased. Overexpression of Rab39b in mouse primary hippocampal neurons demonstrated a significant decrease in neuronal branching as well as in the number of synapses when compared with the control neurons. Taken together, we provide evidence that the increased dosage of RAB39B causes a disturbed neuronal development leading to cognitive impairment in patients with this recurrent copy number gain.

Published
2014

2. RAE-1, a novel PHR binding protein, is required for axon termination and synapse formation in Caenorhabditis elegans

Author

Yishi Jin, Lizhen Chen, Craig C. Garner, Matthew P. Anderson, Scott T. Baker, Erik D. Tulgren, Willy V. Bienvenut, Brock Grill, and Manfredo Quadroni

Subjects
Nucleocytoplasmic Transport Proteins, Ubiquitin-Protein Ligases, Amino Acid Motifs, Molecular Sequence Data, Plasma protein binding, Adaptor Proteins, Signal Transducing/genetics, Adaptor Proteins, Signal Transducing/metabolism, Amino Acid Motifs/genetics, Amino Acid Sequence/genetics, Animals, Animals, Genetically Modified, Axons/physiology, Caenorhabditis elegans, Caenorhabditis elegans Proteins/genetics, Caenorhabditis elegans Proteins/metabolism, F-Box Proteins/genetics, F-Box Proteins/metabolism, Gene Expression Regulation/genetics, Guanine Nucleotide Exchange Factors/genetics, Guanine Nucleotide Exchange Factors/metabolism, Humans, Immunoprecipitation, Luminescent Proteins/genetics, Mass Spectrometry, Mechanoreceptors/cytology, Microscopy, Confocal, Mutation/genetics, Nuclear Matrix-Associated Proteins/deficiency, Nuclear Matrix-Associated Proteins/genetics, Nucleocytoplasmic Transport Proteins/deficiency, Nucleocytoplasmic Transport Proteins/genetics, Protein Binding/genetics, Signal Transduction/genetics, Synapses/genetics, Synapses/physiology, Ubiquitin-Protein Ligases/genetics, Ubiquitin-Protein Ligases/metabolism, rab GTP-Binding Proteins/genetics, rab GTP-Binding Proteins/metabolism, F-box protein, DNA-binding protein, Article, Synapse, Nuclear Matrix-Associated Proteins, medicine, Guanine Nucleotide Exchange Factors, Amino Acid Sequence, Axon, Caenorhabditis elegans Proteins, Adaptor Proteins, Signal Transducing, biology, General Neuroscience, Binding protein, F-Box Proteins, Signal transducing adaptor protein, biology.organism_classification, equipment and supplies, Axons, Cell biology, Luminescent Proteins, medicine.anatomical_structure, Gene Expression Regulation, rab GTP-Binding Proteins, Mutation, Synapses, biology.protein, Mechanoreceptors, Protein Binding, Signal Transduction
Abstract

Previous studies inCaenorhabditis elegansshowed that RPM-1 (Regulator of Presynaptic Morphology-1) regulates axon termination and synapse formation. To understand the mechanism of howrpm-1functions, we have used mass spectrometry to identify RPM-1 binding proteins, and have identified RAE-1 (RNA Export protein-1) as an evolutionarily conserved binding partner. We define a RAE-1 binding region in RPM-1, and show that this binding interaction is conserved and also occurs between Rae1 and the human ortholog of RPM-1 called Pam (protein associated with Myc).rae-1loss of function causes similar axon and synapse defects, and synergizes genetically with two other RPM-1 binding proteins, GLO-4 and FSN-1. Further, we show that RAE-1 colocalizes with RPM-1 in neurons, and thatrae-1functions downstream ofrpm-1. These studies establish a novel postmitotic function forrae-1in neuronal development.

Published
2012

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