reduced expression of the receptor may also be 
due to inefficiency in re-initiation of translation at 
the initiator methionine for the receptor follow- 
ing synthesis of the peptide encoded by the SORF. 
These experiments demonstrate that the receptor 
mRNA is bi-cistronic; the physiologic importance of 
the SORP in regulating /32-receptor expression is yet 
to be determined. 
Intracellular Trafficking of Adrenergic 
Receptors 
Adrenergic receptors are plasma membrane pro- 
teins that permit extracellular catecholamines to in- 
fluence cellular function. However, there is evi- 
dence that in some differentiated cells, such as 
neurons, adrenergic receptors may be targeted to 
specific domains on the plasma membrane. Further- 
more, some adrenergic receptors are reversibly in- 
ternalized following agonist stimulation. Little is 
known about the mechanism by which receptors are 
targeted to specific domains or how targeting is 
modulated by agonists. 
Dr. Mark von Zastrow has been using immunocyto- 
chemical techniques to study adrenergic receptor 
targeting and intracellular trafficking. Following ag- 
onist stimulation, the (82-adrenergic receptor under- 
goes rapid (within minutes) reversible internaliza- 
tion into an endosomal compartment that also 
contains the transferrin receptor. In contrast, the 
receptor undergoes a much slower internalization 
(hours), which is much less extensive. When both 
receptors are expressed in the same cell they are 
predominantly found in the plasma membrane. Fol- 
lowing stimulation by a common agonist (epineph- 
rine or norepinephrine), up to 75% of (82 receptors 
are internalized within 1 5 minutes, while no signifi- 
cant redistribution of a2 receptors is noted. 
In addition to these differences in intracellular 
trafficking, Dr. von Zastrow has observed differ- 
ences in targeting of two highly homologous sub- 
types of the receptor. The mouse homologue of 
the human receptor localized on chromosome 1 0 
is found predominantly on the plasma membrane, 
while that localized on chromosome 4 is found pre- 
dominantly in intracellular vesicles. The biological 
significance of these differences in targeting and 
trafficking is not known; however, these results sug- 
gest that in addition to structural determinants for 
ligand binding and G protein activation, receptors 
can be distinguished by determinants that differen- 
tially link receptors to cytoskeletal and membrane 
transport proteins. Future research will attempt to 
determine physiologic significance of differential 
sorting of receptors and to identify proteins in- 
volved in regulating the trafficking and agonist- 
mediated internalization of receptors. 
Dr. Kobilka is also Assistant Professor of Cardi- 
ology and of Molecular and Cellular Physiology at 
Stanford University School of Medicine. 
Articles 
Guan, X., Peroutka, S.J., and Kobilka, B.K. 1992. 
Identification of a single amino acid residue re- 
sponsible for the binding of a class of /3-adrenergic 
receptor antagonists to 5-hydroxytrptaminelA re- 
ceptors. Mol Pharmacol 41:695-698. 
Kobilka, B.K. 1991- Molecular and cellular biol- 
ogy of adrenergic receptors. Trends Cardiovasc 
Med 1:189-194. 
Kobilka, B.K. 1992. Adrenergic receptors as mod- 
els for G protein-coupled receptors. Annu Rev 
Neurosci 15:87-114. 
Link, R., Daunt, D., Barsh, G., Chruscinski, A., and 
Kobilka, B.K. 1992. Cloning of two mouse genes 
encoding Q!2-adrenergic receptor subtypes and 
identification of a single amino acid in the mouse 
a2-C10 homolog responsible for an interspecies 
variation in antagonist binding. Mol Pharmacol 
42:16-27. 
von Zastrow, M., and Kobilka, B.K. 1992. Ligand- 
regulated internalization and recycling of human 
/32-adrenergic receptors between the plasma 
membrane and endosomes containing transferrin 
receptors./ 5/0/ Chem 267:3530-3538. 
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