Adrenergic Receptor Structure and Function 
structure and may identify factors that will en- 
hance the production of functional protein. 
Using a cell-free expression system developed 
in my laboratory, we have characterized the in- 
sertion of specific membrane-spanning domains 
into the lipid bilayer. The proper insertion of the 
first membrane-spanning domain is relatively in- 
efficient. Using recombinant DNA techniques, 
we have identified a structural modification that 
enhances the integration of this domain and in- 
creases the amount of functional ^2 receptor pro- 
tein expressed in cultured cells. 
We have previously shown that ^2 receptor is 
nonfunctional immediately after translation and 
translocation into the endoplasmic reticulum. 
Our studies indicate that additional cytosolic and 
membrane factors are required to process the re- 
ceptor to a functional form. We are attempting to 
identify structural differences between a func- 
tional receptor and newly synthesized receptors 
that have not undergone the post-translational 
processing necessary to produce functional pro- 
tein. We hope to identify the requisite cytosolic 
and membrane factors. 
Cellular Biology of /82-Adrenergic Receptors 
Following prolonged exposure to catechol- 
amines, the ;82-adrenergic receptor becomes de- 
sensitized and is less efficient in activating adeny- 
lyl cyclase. Several mechanisms contribute to the 
process of desensitization, including receptor 
phosphorylation and the removal of receptors 
from the plasma membrane. Over the past year 
we have used immunocytochemical techniques 
to study agonist-mediated internalization of ^2- 
adrenergic receptors. These studies confirm that 
these receptors are rapidly internalized into in- 
tracellular vesicles called early endosomes. We 
plan to continue our efforts to determine the 
mechanism by which this occurs and to identify 
the cellular proteins that mediate this process. 
Furthermore, we hope to gain a better under- 
standing of the relative importance of agonist- 
activated internalization in the physiology of 
182-adrenergic receptors. 
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