Role of Rab11 in the mTOR-mediated autophagy in the dendritic spines

• Autorzy: Janusz-Kaminska A. , Switon K. , Jaworski J.
• Języki publikacji: EN

Abstrakty

EN

INTRODUCTION: Rab11a is a protein that belongs to the small GTPase superfamily. It is known to be involved in the endocytic recycling. In neurons, it was demonstrated to participate in TrkB receptor translocation to the postsynaptic density in the chemical long-term potentiation (c-LTP) upon BDNF stimulation and in AMPA receptor recycling. Recycling endosomes were also shown to contribute to early steps in autophagy, and Rab11 depletion inhibited autophagosome formation in human HEK293A cells. Lack of mTOR-driven autophagy was implied to cause defective dendritic spine pruning and faulty synaptic plasticity in autistic spectrum disorders. AIM(S): We sought to investigate how Rab11 strikes a balance between endocytic recycling and autophagy in synaptic plasticity via mTOR dependent pathway. METHOD(S): So far, we have performed live imaging of primary hippocampal neurons on the confocal spinning disc microscope to estimate the mobility of Rab11-mCherry in the dendritic spines. By super-resolution immunofluorescence imaging we have investigated colocalization of Rab11a with early autophagy marker Atg9a, recycling endosome marker syntaxin13 and Hook 1 protein in the dendritic spines. We have also co-immunoprecipitated EGFP-Rab11 with myc-mTOR. RESULTS: We have shown that Rab11 vesicles decrease their mobility upon mTOR inhibition in the dendritic spines of primary hippocampal neurons. We have also confirmed that EGFP-Rab11 is pulled down with myc-mTOR in the immunoprecipitation experiment. Preliminary analysis indicated increased Rab11 colocalization with autophagy markers upon mTOR inhibition. CONCLUSIONS: Altogether our results point to the potential role of Rab11 in the mTOR-dependent autophagy in the synaptic plasticity. FINANCIAL SUPPORT: This research was funded by Polish National Science Centre Sonata Bis (2012/07/E/ NZ3/00503).

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2017
• Tom: 77
• Numer: Suppl.1
• Opis fizyczny: p.62

Twórcy

autor

Janusz-Kaminska A.

• International Institute of Molecular and Cell Biology, Laboratory of Molecular and Cell Neurobiology, Warsaw, Poland

autor

Switon K.

• International Institute of Molecular and Cell Biology, Laboratory of Molecular and Cell Neurobiology, Warsaw, Poland

autor

Jaworski J.

• International Institute of Molecular and Cell Biology, Laboratory of Molecular and Cell Neurobiology, Warsaw, Poland