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The Journal of Neuroscience, November 1, 1999, 19(21):9281-9288
Receptor Subtype-Induced Targeting and Subtype-Specific
Internalization of Human  2-Adrenoceptors in PC12
Cells
Tuire
Olli-Lähdesmäki1, 2, 3,
Jaana
Kallio1, 2, and
Mika
Scheinin1, 2
1 Department of Pharmacology and Clinical Pharmacology,
2 Medicity Research Laboratories, and 3 Turku
Graduate School of Biomedical Sciences, University of Turku, FIN-20520
Turku, Finland
The three  2-adrenergic receptor subtypes have
distinct tissue distributions, desensitization properties, and, in some
cell types, subtype-specific subcellular localization and trafficking properties. The subtypes also differ in their neuronal physiology. Therefore, we have investigated the localization and targeting of human
2-adrenoceptors (2-AR) in PC12 cells,
which were transfected to express the 2-AR subtypes A,
B, and C. Inspection of the receptors by indirect immunofluorescence
and confocal microscopy showed that 2A-AR were mainly
targeted to the tips of the neurites, 2B-AR were evenly
distributed in the plasma membrane, and 2C-AR were
mostly located in an intracellular perinuclear compartment. After
agonist treatment, 2A- and 2B-AR were
internalized into partly overlapping populations of intracellular
vesicles. Receptor subtype-specific changes in PC12 cell morphology
were also discovered: expression of 2A-AR, but not of
2B- or 2C-AR, induced
differentiation-like changes in cells not treated with NGF. Also
2B-AR were targeted to the tips of neurites when they
were coexpressed in the same cells with 2A-AR,
indicating that the targeting of receptors to the tips of neurites is a
consequence of a change in PC12 cell membrane protein trafficking that
the 2A-subtype induces. The marked agonist-induced
internalization of 2A-AR observed in both nondifferentiated and differentiated PC12 cells contrasts with earlier
results from non-neuronal cells and points out the importance of the
cellular environment for receptor endocytosis and trafficking. The
targeting of 2A-AR to nerve terminals in PC12 cells is
in line with the putative physiological role of this receptor subtype as a presynaptic autoreceptor.
Key words:
2-adrenoceptors; endocytosis; internalization; differentiation; PC12 cells; immunocytochemistry; targeting
Copyright © 1999 Society for Neuroscience 0270-6474/99/19219281-08$05.00/0
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