Role of Amot12, Rast8 and Homer1 in the organization of postsynaptic machinery

• Autorzy: Gawor M. , Niewiadomski P. , Bernadzki K. , Jozwiak J. , Rojek K. , Redowicz M.J. , Proswzynski T.J.
• Języki publikacji: EN

Abstrakty

EN

BACKGROUND AND AIMS: Vertebrate neuromuscular junction (NMJ) undergoes a series of topological rearrangements in order to achieve its mature complex shape resembling pretzels. We have previously reported that podosomes, actin-rich dynamic adhesive organelles are implicated in the NMJ developmental remodeling. The main aim of this study was to understand molecular mechanisms regulating formation of podosomes and/or remodeling of the postsynaptic machinery with a special focus on the role of Amotl2 scaffold protein in these processes. METHODS: To identify Amotl2-binding proteins we used TAP-tag affinity purification and mass spectrometry. Localization of proteins to NMJ subsynaptic compartments was performed using standard cytochemical procedures and confocal microscopy. We performed RNAi-based knockdown experiments on cultured C21C12 myotubes to assess the importance of proteins in the organization of postsynaptic AChR clusters. RESULTS: We identified several novel Amotl2-binding proteins and subsequently focused our experiments on two of them, Rassf8 and Homer1, that remain uncharacterized at the NMJ. Amotl2, Rassf8 and Homer1 are concentrated at postsynaptic areas of NMJs in the indentations between the AChR-rich branches. Our results suggest that Rassf8 and Homer1 may be involved in AChR organization and development of the neuromuscular synapses. CONCLUSIONS: We identified novel components of the muscle postsynaptic machinery that specifically localize to the sites of NMJ remodeling. Our results suggest that Amotl2 may be involved in the developmental remodeling of the postsynaptic machinery through the interactions with Rassf8 and Homer1. This research was supported by the NCN grant 2012/05/E/ NZ3/00487.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2015
• Tom: 75
• Numer: Supl.
• Opis fizyczny: p.S75-S76

Twórcy

autor

Gawor M.

• Laboratory of Synaptogenesis, Department of Cell Biology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland

autor

Niewiadomski P.

• Laboratory of Synaptogenesis, Department of Cell Biology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland

autor

Bernadzki K.

• Laboratory of Synaptogenesis, Department of Cell Biology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland

autor

Jozwiak J.

• Laboratory of Cell Motility, Department of Biochemistry, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland

autor

Rojek K.

• Laboratory of Synaptogenesis, Department of Cell Biology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland

autor

Redowicz M.J.

• Laboratory of Cell Motility, Department of Biochemistry, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland

autor

Proswzynski T.J.

• Laboratory of Synaptogenesis, Department of Cell Biology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland