Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Nusshold, C; Uellen, A; Bernhart, E; Hammer, A; Damm, S; Wintersperger, A; Reicher, H; Hermetter, A; Malle, E; Sattler, W.
Endocytosis and intracellular processing of BODIPY-sphingomyelin by murine CATH.a neurons.
Biochim Biophys Acta. 2013; 1831(12):1665-1678
Doi: 10.1016/j.bbalip.2013.08.007
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- Leading authors Med Uni Graz
- Nusshold Christoph
- Sattler Wolfgang
- Co-authors Med Uni Graz
- Bernhart Eva Maria
- Damm Sabine
- Hammer Astrid
- Hinteregger Helga
- Malle Ernst
- Üllen Andreas
- Wintersperger Andrea
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- Abstract:
- Neuronal sphingolipids (SL) play important roles during axonal extension, neurotrophic receptor signaling and neurotransmitter release. Many of these signaling pathways depend on the presence of specialized membrane microdomains termed lipid rafts. Sphingomyelin (SM), one of the main raft constituents, can be formed de novo or supplied from exogenous sources. The present study aimed to characterize fluorescently-labeled SL turnover in a murine neuronal cell line (CATH.a). Our results demonstrate that at 4°C exogenously added BODIPY-SM accumulates exclusively at the plasma membrane. Treatment of cells with bacterial sphingomyelinase (SMase) and back-exchange experiments revealed that 55-67% of BODIPY-SM resides in the outer leaflet of the plasma membrane. Endocytosis of BODIPY-SM occurs via caveolae with part of internalized BODIPY-fluorescence ending up in the Golgi and the ER. Following endocytosis BODIPY-SM undergoes hydrolysis, a reaction substantially faster than BODIPY-SM synthesis from BODIPY-ceramide. RNAi demonstrated that both, acid (a)SMase and neutral (n)SMases contribute to BODIPY-SM hydrolysis. Finally, high-density lipoprotein (HDL)-associated BODIPY-SM was efficiently taken up by CATH.a cells. Our findings indicate that endocytosis of exogenous SM occurs almost exclusively via caveolin-dependent pathways, that both, a- and nSMases equally contribute to neuronal SM turnover and that HDL-like particles might represent physiological SM carriers/donors in the brain.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Boron Compounds -
- Caveolins - genetics
- Cell Line -
- Endocytosis -
- Endoplasmic Reticulum - drug effects
- Fluorescent Dyes -
- Gene Expression Regulation -
- Golgi Apparatus - drug effects
- Hydrolysis -
- Isoenzymes - antagonists & inhibitors
- Lipoproteins, HDL - metabolism
- Membrane Microdomains - drug effects
- Mice -
- Neurons - cytology
- RNA, Small Interfering - genetics
- Signal Transduction -
- Sphingomyelin Phosphodiesterase - antagonists & inhibitors
- Sphingomyelins - metabolism
- Temperature -
- Find related publications in this database (Keywords)
- Sphingomyelinase
- High density lipoprotein
- Caveolar uptake
- Endocytosis