Functional implications of novel human acid sphingomyelinase splice variants

Rhein C, Tripal P, Seebahn A, Konrad A, Kramer M, Nagel C, Kemper J, Bode J, Mühle C, Gulbins E, Reichel M, Becker CM, Kornhuber J (2012)

Publication Type: Journal article

Publication year: 2012

Journal

PLoS ONE Public Library of Science

Book Volume: 7

Pages Range: e35467

Journal Issue: 4

DOI: 10.1371/journal.pone.0035467

Abstract

Acid sphingomyelinase (ASM) hydrolyses sphingomyelin and generates the lipid messenger ceramide, which mediates a variety of stress-related cellular processes. The pathological effects of dysregulated ASM activity are evident in several human diseases and indicate an important functional role for ASM regulation. We investigated alternative splicing as a possible mechanism for regulating cellular ASM activity.We identified three novel ASM splice variants in human cells, termed ASM-5, -6 and -7, which lack portions of the catalytic- and/or carboxy-terminal domains in comparison to full-length ASM-1. Differential expression patterns in primary blood cells indicated that ASM splicing might be subject to regulatory processes. The newly identified ASM splice variants were catalytically inactive in biochemical in vitro assays, but they decreased the relative cellular ceramide content in overexpression studies and exerted a dominant-negative effect on ASM activity in physiological cell models.These findings indicate that alternative splicing of ASM is of functional significance for the cellular stress response, possibly representing a mechanism for maintaining constant levels of cellular ASM enzyme activity.

Authors with CRIS profile

Philipp Tripal Department of Surgery Angela Seebahn Lehrstuhl für Biochemie und Molekulare Medizin Christine Nagel Lehrstuhl für Psychiatrie und Psychotherapie Jens Bode Lehrstuhl für Psychiatrie und Psychotherapie Christiane Mühle Department of Psychiatry and Psychotherapy Martin Reichel Department of Psychiatry and Psychotherapy Cord-Michael Becker Medizinische Fakultät Johannes Kornhuber Lehrstuhl für Psychiatrie und Psychotherapie

Involved external institutions

Universität Duisburg-Essen (UDE) DE Germany (DE) Universitätsklinikum Jena DE Germany (DE)

How to cite

APA:

Rhein, C., Tripal, P., Seebahn, A., Konrad, A., Kramer, M., Nagel, C.,... Kornhuber, J. (2012). Functional implications of novel human acid sphingomyelinase splice variants. PLoS ONE, 7(4), e35467. https://dx.doi.org/10.1371/journal.pone.0035467

MLA:

Rhein, Cosima, et al. "Functional implications of novel human acid sphingomyelinase splice variants." PLoS ONE 7.4 (2012): e35467.

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