Purchase this article with an account.
E.-K. Kim, H.-J. Cho, S.-Y. Ahn, Y.-J. Choi, T.-I. Kim, S. Cristol, S.-I. Choi; Lysosomal Traffic and Degradation of ßig-h3 Protein. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5864.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To investigate intracellular traffic and degradation of ßig-h3 protein, a protein associated with amyloid deposition in granular corneal dystrophy Type II (GCDII).
Corneal fibroblasts were treated with proteasomal inhibitors, lactacystin and MG132, or lysosomal inhibitors, bafilomycin A1 for 12 h. We used immunoblot analysis to measure ßig-h3 protein in cell lysate.
The lysosomal inhibitors, bafilomycin A1, significantly blocked ßig-h3 protein degradation in a dose-dependent manner in cultured corneal fibroblasts. In contrast, proteasomal inhibitor, MG132, did not lead to significant accumulation of ßig-h3 protein. The internalization of ßig-h3 is inhibited by nystatin, which blocks lipid raft endocytosis, but not by chlorpromazine which is known to block clathrin-mediated endocytosis. Moreover, ßig-h3 endocytosis was decreased significantly in TGF-ß1-exposed cultured corneal fibroblasts.
These results demonstrate that ßig-h3 protein degradation is mediated by an autophagy/lysosomes pathway. Alterations both in lysosomal degradation and in expression of ßig-h3 induced by TGF-ß1 may contribute to amyloid deposition of ßig-h3 in GCDII.
This PDF is available to Subscribers Only