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01-07-2008 | Short Communication

Dysregulation of large-conductance Ca²⁺-activated K⁺ channel expression in nonsyndromal mental retardation due to a cereblon p.R419X mutation

Authors: Joseph J. Higgins, Jin Hao, Barry E. Kosofsky, Anjali M. Rajadhyaksha

Published in: Neurogenetics | Issue 3/2008

Abstract

A nonsense mutation (R419X) in the human cereblon gene [mutation (mut) CRBN] causes a mild type of autosomal recessive nonsyndromal mental retardation (ARNSMR). CRBN, a cytosolic protein, regulates the assembly and neuronal surface expression of large-conductance Ca²⁺-activated K⁺ channels (BK_Ca) in brain regions involved in memory and learning. Using the real-time quantitative polymerase chain reaction, we show that mut CRBN disturbs the development of adult brain BK_Ca isoforms. These changes are predicted to result in BK_Ca channels with a higher intracellular Ca²⁺ sensitivity, faster activation, and slower deactivation kinetics. Such alterations may contribute to cognitive impairments in patients with mild ARNSMR.

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Title: Dysregulation of large-conductance Ca2+-activated K+ channel expression in nonsyndromal mental retardation due to a cereblon p.R419X mutation
Authors: Joseph J. Higgins
Jin Hao
Barry E. Kosofsky
Anjali M. Rajadhyaksha
Publication date: 01-07-2008
Publisher: Springer Berlin Heidelberg
Published in: Neurogenetics / Issue 3/2008
Print ISSN: 1364-6745
Electronic ISSN: 1364-6753
DOI: https://doi.org/10.1007/s10048-008-0128-2

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Springer Medicine

Dysregulation of large-conductance Ca²⁺-activated K⁺ channel expression in nonsyndromal mental retardation due to a cereblon p.R419X mutation

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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