RT Journal Article
SR Electronic
T1 mTORC1 and mTORC2 regulate distinct aspects of glutamatergic synaptic transmission
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 731554
DO 10.1101/731554
A1 Matthew P. McCabe
A1 Erin R. Cullen
A1 Caitlynn M. Barrows
A1 Amy N. Shore
A1 Katharine I. Tooke
A1 Matthew C. Weston
YR 2019
UL http://biorxiv.org/content/early/2019/08/15/731554.abstract
AB Although mTOR signaling is known as a broad regulator of cell growth and proliferation, in neurons it regulates synaptic transmission, which is thought to be a major mechanism through which altered mTOR signaling leads to neurological disease. Although previous studies have delineated postsynaptic roles for mTOR, whether it regulates presynaptic function is largely unknown. Moreover, the mTOR kinase operates in two complexes, mTORC1 and mTORC2, suggesting that mTOR’s role in synaptic transmission may be complex-specific. To better understand each complex’s role in synaptic transmission, we genetically inactivated mTORC1 or mTORC2 in cultured mouse glutamatergic hippocampal neurons. Inactivation of either complex reduced neuron growth and evoked EPSCs, however, mTORC1 exerted its effects on eEPSCs at the postsynapse and mTORC2 at the presynapse. Furthermore, inactivation of each complex altered specific modes of synaptic vesicle release, suggesting that mTORC1 and mTORC2 differentially modulate postsynaptic responsiveness and presynaptic release to optimize glutamatergic synaptic transmission.