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Journal of Neuroscience, Vol 15, 4140-4147, Copyright © 1995 by Society for Neuroscience
Somatodendritic internalization and perinuclear targeting of neurotensin in the mammalian brain
MP Faure, A Alonso, D Nouel, G Gaudriault, M Dennis, JP Vincent and A Beaudet
Montreal Neurological Institute, Quebec, Canada.
Polypeptide hormones and growth factors have long been known to internalize
into peripheral target cells as a result of their interaction with cell
surface receptors. Studies in culture have suggested that certain
neuropeptides might undergo a similar type of translocation in neurons. To
investigate this possibility in adult mammalian brain, we have examined by
confocal laser microscopy the events that follow the binding of
fluorescein-tagged derivatives of the tridecapeptide neurotensin to basal
forebrain cholinergic cells. Our results demonstrate a selective time- and
temperature-dependent internalization of fluo-neurotensin in these cells.
This internalization is receptor mediated, proceeds from the entire
somatodendritic membrane of the cells, and utilizes endosome-like
organelles which are mobilized from dendrites to perikarya and from the
periphery of the cell to its perinuclear region. Parallel studies carried
out on Sf9 insect cells expressing the rat neurotensin receptor from a
recombinant baculovirus indicated that the internalization process involves
receptor-ligand complexes and not merely the fluorescent peptide itself.
These data suggest that receptor internalization plays a role in
neuropeptide signaling in the brain and that it can be harnessed for
selective identification of neuropeptide target cells.
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