Mutual effects of caveolin and nerve growth factor signaling in pig oligodendrocytes

Signaling of growth factors may depend on the recruitment of their receptors to specialized microdomains. Previous reports on PC12 cells indicated an interaction of raft‐organized caveolin and TrkA signaling. Because porcine oligodendrocytes (OLs) respond to nerve growth factor (NGF), we were intere...

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Published in:Journal of neuroscience research 2010-02, Vol.88 (3), p.572-588
Main Authors: Schmitz, Matthias, Klöppner, Sabine, Klopfleisch, Steve, Möbius, Wiebke, Schwartz, Peter, Zerr, Inga, Althaus, Hans H.
Format: Article
Language:English
Subjects:
Animals
Brain - metabolism
caveolae
caveolin
Caveolin 1 - genetics
Caveolin 1 - metabolism
caveolin knockdown
Caveolins - genetics
Caveolins - metabolism
Cell Membrane - metabolism
Cells, Cultured
cholesterol
Down-Regulation
Gene Knockdown Techniques
Intracellular Space - metabolism
MAPK
Mitogen-Activated Protein Kinases - metabolism
Myelin Sheath - metabolism
Nerve Growth Factor - metabolism
NGF
oligodendrocytes
Oligodendroglia - metabolism
Phosphorylation
Proto-Oncogene Proteins p21(ras) - metabolism
Receptor, trkA - metabolism
RNA, Small Interfering
Signal Transduction
Swine
TrkA
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Summary:Signaling of growth factors may depend on the recruitment of their receptors to specialized microdomains. Previous reports on PC12 cells indicated an interaction of raft‐organized caveolin and TrkA signaling. Because porcine oligodendrocytes (OLs) respond to nerve growth factor (NGF), we were interested to know whether caveolin also plays a role in oligodendroglial NGF/TrkA signaling. OLs expressed caveolin at the plasma membrane but also intracellularly. This was partially organized in the classically Ω‐shaped invaginations, which may represent caveolae. We could show that caveolin and TrkA colocalize by using a discontinuous sucrose gradient (Song et al. [1996] J. Biol. Chem. 271:9690–9697), MACS technology, and immunoprecipitation. However, differential extraction of caveolin and TrkA with Triton X‐100 at 4°C indicated that caveolin and TrkA are probably not exclusively present in detergent‐resistant, caveolin‐containing rafts (CCRs). NGF treatment of OLs up‐regulated the expression of caveolin‐1 (cav‐1) and stimulated tyrosine‐14 phosphorylation of cav‐1. Furthermore, OLs were transfected with cav‐1‐specific small interfering RNA (siRNA). A knockdown of cav‐1 resulted in a reduced activation of downstream components of the NGF signaling cascade, such as p21Ras and mitogen‐activated protein kinase (MAPK) after NGF exposure of OLs. Subsequently, increased oligodendroglial process formation via NGF was impaired. The present study indicates that CCRs/caveolin could play a modulating role during oligodendroglial differentiation and regeneration. © 2009 Wiley‐Liss, Inc.
ISSN:0360-4012
1097-4547
1097-4547
DOI:10.1002/jnr.22235