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Endocytosis of Prion Protein Is Required for ERK1/2 Signaling Induced by Stress-Inducible Protein 1.
- Source :
- Journal of Neuroscience; 6/25/2008, Vol. 28 Issue 26, p6691-6702, 12p, 3 Color Photographs, 5 Graphs
- Publication Year :
- 2008
-
Abstract
- The secreted cochaperone STI1 triggers activation of protein kinase A (PKA) and ERK1/2 signaling by interacting with the cellular prion (PrP<superscript>C</superscript>) at the cell surface, resulting in neuroprotection and increased neuritogenesis. Here, we investigated whether STI1 triggers PrP<superscript>C</superscript> trafficking and tested whether this process controls PrP<superscript>C</superscript>-dependent signaling. We found that STI1, but not a STI1 mutant unable to bind PrP<superscript>C</superscript>, induced PrP<superscript>C</superscript> endocytosis. STI1-induced signaling did not occur in cells devoid of endogenous PrP<superscript>C</superscript>; however, heterologous expression of PrP<superscript>C</superscript> reconstituted both PKA and ERK1/2 activation. In contrast, a PrP<superscript>C</superscript> mutant lacking endocytic activity was unable to promote ERK1/2 activation induced by STI1, whereas it reconstituted PKA activity in the same condition, suggesting a key role of endocytosis in the former process. The activation of ERK1/2 by STI1 was transient and appeared to depend on the interaction of the two proteins at the cell surface or shortly after internalization. Moreover, inhibition of dynamin activity by expression of a dominant-negative mutant caused the accumulation and colocalization of these proteins at the plasma membrane, suggesting that both proteins use a dynamin-dependent internalization pathway. These results show that PrP<superscript>C</superscript> endocytosis is a necessary step to modulate STI1-dependent ERK1/2 signaling involved in neuritogenesis. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 02706474
- Volume :
- 28
- Issue :
- 26
- Database :
- Complementary Index
- Journal :
- Journal of Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 32919302
- Full Text :
- https://doi.org/10.1523/JNEUROSCI.1701-08.2008