Absence of TI-VAMP/Vamp7 Leads to Increased Anxiety in Mice

Danglot, Lydia; Zylbersztejn, Kathleen; Petković, Maja; Gauberti, Maxime; Méziane, Hamid; Combe, Roy; Champy, Marie‐France; Birling, Marie‐Christine; Pavlovic, Guillaume; Bizot, Jean-Charles; Trovero, Fabrice; Ragione, Floriana Della; Proux-Gillardeaux, Véronique; Sorg, Tania; Vivien, Denis; D’Esposito, Maurizio; Galli, Thierry

doi:10.1523/jneurosci.4436-11.2012

Cited by 63 publications

(69 citation statements)

References 36 publications

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“…In conclusion, VAMP7 KO MEFs show phenotypes clearly related to the traffic of lipids and proteins known to reside in membrane domains. While these phenotypic traits do not preclude cell and organism life, 55,56 they may nevertheless induce profound signaling defects 20 which largely remain to explore. Further studies are required to address the impact of this mechanism in the organism and also how a v-SNARE which primarily mediates membrane fusion may also be required at earlier stages of membrane traffic like sorting of some components of membrane domains.…”

Section: Discussionmentioning

confidence: 99%

“…56 All animals were handled in strict accordance with good animal practice as defined by the national and/or local animal welfare bodies including local Ethics Committee (called CEEA40-Comite d' ethique Buffon at the Ministry of Higher Education and Research), and all mouse work was approved by the Veterinary Services of Paris (Authorization number: 75-1073). Because VAMP7 gene is located on the X chromosome, only male embryos were used for cell culture.…”

Section: Methodsmentioning

confidence: 99%

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Role of tetanus neurotoxin insensitive vesicle-associated membrane protein in membrane domains transport and homeostasis

et al. 2015

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Keywords: exocytosis, Golgi apparatus, SNARE, sphingolipids, TI-VAMP/VAMP7 Abbreviations: BFA, Brefeldin A; Cer, Ceramide; ER, Endoplasmic Reticulum; GlcCer, Glucosylceramide; GM3, ganglioside monosialic acid 3; GPI, Glycosylphosphatidylinositol; GSL, Glycosphingolipids; LC, Long Chain; PI, Phosphatidylinositide; PM, Plasma Membrane; SM, Sphingomyelin; TGN, D Trans-Golgi Network; TI-VAMP/VAMP7, Tetanus neurotoxin-insensitive vesicle-associated membrane protein / Vesicle associated membrane protein 7; VLC, very long vhain; VSVG, Vesicular Stomatitis Virus GlycoproteinBiological membranes in eukaryotes contain a large variety of proteins and lipids often distributed in domains in plasma membrane and endomembranes. Molecular mechanisms responsible for the transport and the organization of these membrane domains along the secretory pathway still remain elusive. Here we show that vesicular SNARE TI-VAMP/VAMP7 plays a major role in membrane domains composition and transport. We found that the transport of exogenous and endogenous GPI-anchored proteins was altered in fibroblasts isolated from VAMP7-knockout mice. Furthermore, disassembly and reformation of the Golgi apparatus induced by Brefeldin A treatment and washout were impaired in VAMP7-depleted cells, suggesting that loss of VAMP7 expression alters biochemical properties and dynamics of the Golgi apparatus. In addition, lipid profiles from these knockout cells indicated a defect in glycosphingolipids homeostasis. We conclude that VAMP7 is required for effective transport of GPI-anchored proteins to cell surface and that VAMP7-dependent transport contributes to both sphingolipids and Golgi homeostasis.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Role of tetanus neurotoxin insensitive vesicle-associated membrane protein in membrane domains transport and homeostasis

et al. 2015

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“…44 Loss of VAMP-7 did not result in any overt developmental or neurologic deficits, although decreased brain weight and increased anxiety in behavioral studies have been reported. 44 Complete blood counts were performed to identify any gross abnormalities in hematopoiesis.…”

Section: Morphologic Comparison Of Wild-type and Vamp-7mentioning

confidence: 87%

“…44 Briefly, loxP sequences were inserted at the borders of exon 3 of VAMP7 to create a VAMP7 floxed allele. VAMP7 flox/flox mice were then crossed with a deleter line expressing Cre recombinase, with the resultant deletion of exon 3.…”

Section: Animalsmentioning

confidence: 99%

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VAMP-7 links granule exocytosis to actin reorganization during platelet activation

Koseoglu

Peters

Fitch-Tewfik

et al. 2015

Blood

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Behavioral Testing Design for Evaluation of Cognitive Disabilities

et al. 2022

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Intellectual disabilities (ID) constitute a class of human neurodevelopmental diseases and are a major medical and socioeconomic problem owing to their high incidence and enormous burden to the families of those affected. In the past three decades, mutant mouse technologies have provided powerful tools for elucidating the pathophysiological mechanisms underlying behavioral and developmental alterations related to IDs and for addressing new therapeutic strategies, and major progress has been made revealing previously unidentified genes involved in ID. However, the pathological hallmarks of IDs are very heterogeneous in regard to both the functional deficits observed and the severity of the phenotype, even within the same mutation types. For this reason, an appropriate experimental design is required to reduce the risk of false negatives and positives in animal functional genomic studies. This experimental design should address functions important to evaluate, tests, and the appropriate workflow. Here, we propose an extensive behavioral screen with detailed protocols, which was successfully used in a systematic mouse functional genomic approach to gain pathway-based insights into mechanisms leading to cognitive dysfunction in humans.

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Absence of TI-VAMP/Vamp7 Leads to Increased Anxiety in Mice

Abstract: Vesicular (v)-and target (t)-SNARE proteins assemble in SNARE complex

Cited by 63 publications

References 36 publications

Role of tetanus neurotoxin insensitive vesicle-associated membrane protein in membrane domains transport and homeostasis

Role of tetanus neurotoxin insensitive vesicle-associated membrane protein in membrane domains transport and homeostasis

VAMP-7 links granule exocytosis to actin reorganization during platelet activation

Behavioral Testing Design for Evaluation of Cognitive Disabilities

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