| 1. |
- Howes, Mark T, et al.
(författare)
-
Clathrin-independent carriers form a high capacity endocytic sorting system at the leading edge of migrating cells
- 2010
-
Ingår i: Journal of Cell Biology. - : Rockefeller University Press. - 0021-9525 .- 1540-8140. ; 190:4, s. 675-691
-
Tidskriftsartikel (refereegranskat)abstract
- Although the importance of clathrin- and caveolin-independent endocytic pathways has recently emerged, key aspects of these routes remain unknown. Using quantitative ultrastructural approaches, we show that clathrin-independent carriers (CLICs) account for approximately three times the volume internalized by the clathrin-mediated endocytic pathway, forming the major pathway involved in uptake of fluid and bulk membrane in fibroblasts. Electron tomographic analysis of the 3D morphology of the earliest carriers shows that they are multidomain organelles that form a complex sorting station as they mature. Proteomic analysis provides direct links between CLICs, cellular adhesion turnover, and migration. Consistent with this, CLIC-mediated endocytosis of key cargo proteins, CD44 and Thy-1, is polarized at the leading edge of migrating fibroblasts, while transient ablation of CLICs impairs their ability to migrate. These studies provide the first quantitative ultrastructural analysis and molecular characterization of the major endocytic pathway in fibroblasts, a pathway that provides rapid membrane turnover at the leading edge of migrating cells.
|
|
| 2. |
- Mattsson, Charlotte L., 1978-
(författare)
-
Role of caveolin-1 in brown adipose tissue
- 2010
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Caveolae are 50-100 nm invaginations in the plasma membrane. Caveolae and the protein caveolin-1 (Cav1) have been shown to be important in many signaling pathways in different cell types; however, in some cell types caveolae and Cav1 do not seem to affect the investigated signaling pathways. In my thesis, I have investigated the role of caveolin-1 (Cav1) in metabolism and b3-adrenergic, LPA-, EGF- and PDGF-receptor signaling in brown adipocytes. Brown adipose tissue is responsible for nonshivering thermogenesis. Recent studies have shown that not only infants but also adult man can have brown adipose tissue and that the presence is negatively correlated with both obesity and age. By understanding how signaling for proliferation and differentiation in brown adipocytes is regulated, it could be possible in the future to activate brown adipose tissue to combat obesity and the metabolic syndrome. In brown adipocytes, both epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) were able to induce proliferation, which was dependent on Erk1/2 activation. However, EGF and PDGF utilized different pathways to activate Erk1/2, with EGF signaling partially occurring via a Src-pathway (not involving PI3K/PKC) and PDGF via a PI3K/PKC/Src-pathway. Furthermore, LPA receptors were able to activate Erk1/2 via two pathways, one Gi/PKC/Src-pathway and one PI3K-pathway. For these receptors, Cav1-ablation did not affect the agonist-induced Erk1/2 activation. Cav1 was, however, required for proper b3-adrenergic receptor (b3-AR) signaling to cAMP and for adenylyl cyclase activity. In Cav1-ablated mice, the adrenergic receptors are desensitized. However, this desensitization could be overcome physiologically, and the Cav1-ablated mice were therefore able to survive in prolonged cold by nonshivering thermogenesis. In conclusion, ablation of Cav1 affected certain signaling pathways in brown adipocytes, while other pathways were not affected or could be physiologically rescued.
|
|
