Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Gauster, M; Siwetz, M; Orendi, K; Moser, G; Desoye, G; Huppertz, B.
Caspases rather than calpains mediate remodelling of the fodrin skeleton during human placental trophoblast fusion.
Cell Death Differ. 2010; 17(2): 336-345.
Doi: 10.1038/cdd.2009.133
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- Führende Autor*innen der Med Uni Graz
- Gauster Martin
- Co-Autor*innen der Med Uni Graz
- Aubell Kristina
- Desoye Gernot
- Huppertz Berthold
- Moser Gerit
- Siwetz Monika
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- Abstract:
- Fusion of cytotrophoblasts with the overlying syncytiotrophoblast is an integral step in differentiation of the human placental villous trophoblast. Multiple factors, such as growth factors, hormones, cytokines, protein kinases, transcription factors and structural membrane proteins, were described to modulate trophoblast fusion. However, the knowledge on remodelling of the membrane-associated cytoskeleton during trophoblast fusion is very limited. This study describes the link between remodelling of spectrin-like alpha-fodrin and intercellular trophoblast fusion. Experiments with primary trophoblasts isolated from term placentas and the choriocarcinoma cell line BeWo revealed a biphasic strategy of the cells to achieve reorganization of alpha-fodrin. Syncytialization of trophoblasts was accompanied by down-regulation of alpha-fodrin mRNA, whereas the full-length alpha-fodrin protein was cleaved into 120 and 150 kDa fragments. Application of calpeptin and calpain inhibitor III did not affect alpha-fodrin fragmentation in primary term trophoblasts and forskolin-treated BeWo cells, but decreased secretion of beta human chorionic gonadotropin. In contrast, inhibitors of caspases 3, 8 and 9 attenuated generation of the 120 kDa fragment and a general caspase inhibitor completely blocked fragmentation, suggesting an exclusive function of caspases in alpha-fodrin remodelling. Immunofluorescence double staining of human placenta revealed co-localization of active caspase 8 with alpha-fodrin positive vesicles in fusing villous cytotrophoblasts. These results suggest that caspase-dependent fragmentation of alpha-fodrin may be important for reorganization of the sub-membranous cytoskeleton during trophoblast fusion.
- Find related publications in this database (using NLM MeSH Indexing)
- Calpain - antagonists and inhibitors Calpain - metabolism
- Carrier Proteins - genetics Carrier Proteins - metabolism
- Caspase 3 - antagonists and inhibitors Caspase 3 - metabolism
- Caspase 8 - antagonists and inhibitors Caspase 8 - metabolism
- Caspase 9 - antagonists and inhibitors Caspase 9 - metabolism
- Caspases - antagonists and inhibitors Caspases - metabolism
- Cell Differentiation - physiology
- Cells, Cultured -
- Chorionic Gonadotropin - metabolism Chorionic Gonadotropin - secretion
- Cytoskeleton - metabolism
- Down-Regulation - physiology
- Enzyme Inhibitors - pharmacology
- Female -
- Humans -
- Membrane Fusion - drug effects Membrane Fusion - physiology
- Microfilament Proteins - genetics Microfilament Proteins - metabolism
- Oxygen - metabolism
- Pregnancy -
- RNA, Messenger - metabolism
- Trophoblasts - cytology Trophoblasts - enzymology Trophoblasts - secretion
- Find related publications in this database (Keywords)
- human placenta
- trophoblast differentiation
- trophoblast fusion