Functional implications of novel human acid sphingomyelinase splice variants.

PloS One
Cosima RheinJohannes Kornhuber

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.

References

Sep 30, 1991·Biochemical and Biophysical Research Communications·K FerlinzK Sandhoff
May 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·O LevranE H Schuchman
Aug 1, 1989·Plant Molecular Biology·D Laflamme, R Roxby
Dec 14, 1987·Biochimica Et Biophysica Acta·L E QuinternK Sandhoff
Feb 1, 1966·Proceedings of the National Academy of Sciences of the United States of America·R O BradyD S Fredrickson
Jan 1, 1996·Experimental Gerontology·B Lecka-CzernikS Goldstein
Oct 1, 1996·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·S Spiegel, A H Merrill
Jan 7, 1998·The Journal of Experimental Medicine·A Haimovitz-FriedmanR Kolesnick
Jul 21, 1998·Annals of the New York Academy of Sciences·S SpiegelF Wang
Mar 18, 2000·The Journal of Biological Chemistry·T LinD R Green
Jul 29, 2000·Methods in Enzymology·E Gulbins, R Kolesnick
Jul 28, 2001·Progress in Neurobiology·P J Grabowski, D L Black
Aug 31, 2002·Nucleic Acids Research·Qiang XuChristopher Lee
Oct 9, 2002·American Journal of Human Genetics·Calogera M SimonaroEdward H Schuchman
Dec 6, 2002·Nature·Y OkazakiUNKNOWN RIKEN Genome Exploration Research Group Phase I & II Team
Jan 18, 2003·The Journal of Clinical Investigation·Carmen García-RuizJosé C Fernández-Checa
Jun 13, 2003·The Journal of Biological Chemistry·Huawei QiuScott M Van Patten
Jul 9, 2004·Annals of the New York Academy of Sciences·Marjorie PickHermona Soreq
Jan 20, 2005·Gene·Stefan StammHermona Soreq
Oct 26, 2005·Journal of Neural Transmission·J KornhuberE Gulbins
Oct 3, 2006·The Journal of Pediatrics·Melissa P WassersteinMargaret M McGovern
Feb 17, 2007·The Journal of Biological Chemistry·Youssef H Zeidan, Yusuf A Hannun
Nov 6, 2007·Genes & Development·John A CalarcoBenjamin J Blencowe
Mar 25, 2008·The Journal of Biological Chemistry·Charmi ShahFahumiya Samad
Jun 13, 2008·Neurobiology of Aging·Xingxuan HeEdward H Schuchman
Oct 29, 2009·Alcoholism, Clinical and Experimental Research·Martin ReichelJohannes Kornhuber
Aug 20, 2010·RNA·Adonis SkandalisMiriam H Richards
May 3, 2011·Cellular and Molecular Life Sciences : CMLS·Jean-Philip TrumanSamar M Hammad

❮ Previous
Next ❯

Citations

Aug 8, 2014·Molecular Neurobiology·Hao DengJoseph Jankovic
Apr 22, 2015·PloS One·Marcel KramerRalf A Claus
May 10, 2013·PloS One·Christiane MühleJohannes Kornhuber
Feb 13, 2017·Journal of Affective Disorders·Adam DinoffKrista L Lanctôt
Dec 26, 2016·Journal of Chromatography. a·Christiane Mühle, Johannes Kornhuber
Nov 23, 2017·Nature Reviews. Molecular Cell Biology·Yusuf A Hannun, Lina M Obeid
Jun 16, 2019·Journal of Clinical Medicine·Christiane MühleJohannes Kornhuber
Jun 3, 2021·International Journal of Molecular Sciences·Cosima RheinJohannes Kornhuber

❮ Previous
Next ❯

Datasets Mentioned

BETA
HQ132746
GM19204

Methods Mentioned

BETA
electrophoresis
transfection
PMA
density gradient centrifugation
PCR
FCS

Software Mentioned

SPSS Statistics
QuantityOne
ClustalW
LightCycler® 480
MIQE

Related Concepts

Related Feeds

Alzheimer's Disease: Transcription

Impaired transcription is associated with the pathogenesis and progression of conditions such as Alzheimer's disease (AD). Here are the latest discoveries pertaining to transcription and AD.

Alternative splicing

Alternative splicing a regulated gene expression process that allows a single genetic sequence to code for multiple proteins. Here is that latest research.