Skip to Content
Merck
  • Preliminary functional assessment and classification of DEPDC5 variants associated with focal epilepsy.

Preliminary functional assessment and classification of DEPDC5 variants associated with focal epilepsy.

Human mutation (2014-11-05)
Melissa van Kranenburg, Marianne Hoogeveen-Westerveld, Mark Nellist
ABSTRACT

The mechanistic target of rapamycin complex 1 (TORC1) senses nutrient availability to regulate eukaryotic anabolic metabolism. In response to limiting concentrations of amino acids, TORC1 kinase activity is inhibited through the GATOR-1 complex. Mutations in DEPDC5, that encodes one of the components of the GATOR-1 complex, have recently been associated with different forms of focal epilepsy. Here, we investigate the effects of 10 DEPDC5 variants identified in individuals with focal epilepsy and two DEPDC5 variants identified in serous ovarian tumors, on TORC1 signaling and GATOR-1 complex formation. According to our functional assessment, three variants clearly disrupted the DEPDC5-dependent inhibition of TORC1. We did not obtain functional evidence to support pathogenicity in the remaining cases. The observed functional differences between the DEPDC5 variants might underlie some of the clinical differences observed in the individuals carrying the different variants.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
HEPES, anhydrous, free-flowing, Redi-Dri, ≥99.5%
Sigma-Aldrich
HEPES, ≥99.5% (titration)
Sigma-Aldrich
HEPES, BioPerformance Certified, ≥99.5% (titration), suitable for cell culture
Sigma-Aldrich
HEPES, BioXtra, suitable for mouse embryo cell culture, ≥99.5% (titration)
Sigma-Aldrich
HEPES, BioXtra, pH 5.0-6.5 (1 M in H2O), ≥99.5% (titration)
Sigma-Aldrich
Sodium Fluoride Solution
Sigma-Aldrich
HEPES, BioUltra, for molecular biology, ≥99.5% (T)
Sigma-Aldrich
3-[(3-Cholamidopropyl)dimethylammonio]-1-propanesulfonate hydrate, 98%
Supelco
HEPES, Pharmaceutical Secondary Standard; Certified Reference Material
SAFC
HEPES
SAFC
HEPES
Sigma-Aldrich
Sodium fluoride 0.5 M solution
Sigma-Aldrich
Sodium fluoride, anhydrous, powder, 99.99% trace metals basis
Supelco
Fluoride ion solution for ISE, 0.1 M F-, analytical standard (for ion-selective electrodes)
Sigma-Aldrich
Sodium fluoride, 99.99% trace metals basis
Sigma-Aldrich
HEPES buffer solution, 1 M in H2O
Sigma-Aldrich
Sodium fluoride, BioXtra, ≥99%
Sigma-Aldrich
Sodium fluoride, BioReagent, suitable for insect cell culture, ≥99%
Supelco
Sodium Fluoride, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Sodium fluoride, puriss., meets analytical specification of Ph. Eur., BP, USP, 98.5-100.5% (calc. to the dried substance)
Sigma-Aldrich
Sodium fluoride, ReagentPlus®, ≥99%
Sigma-Aldrich
Sodium fluoride, ACS reagent, ≥99%