III. Signals Mediating Receptor Recycling. 
In general, cell surface receptors capable of 
being internalized can be divided into two classes— 
those that recycle back to the surface and those 
that do not. LDL receptors and MHC class I mole- 
cules belong to the first class; the T cell surface 
molecule CD4 belongs to the second. Although it is 
known that the extracellular domain can be a fac- 
tor in determining a receptor's fate subsequent to 
internalization, a possible role for the cytoplasmic 
domain has not been examined. Dr. Davis and his 
colleagues have found that splicing the transmem- 
brane and cytoplasmic domains of the LDL receptor 
to the A2.1 extracellular domain allows recycling, 
whereas splicing the corresponding domains from 
CD4 to the extracellular domain of either A2.1 or 
LDL receptor confers phorbol 12-myristate 13-ace- 
tate (PMA)-inducible internalization but does not 
allow recycling. Thus it appears that the cytoplas- 
mic domain can play a role in determining whether 
an endocytosed receptor recycles to the surface or 
is targeted for intracellular degradation, at least in 
the case of CD4. 
Dr. Davis is also Assistant Professor of Medicine 
and of Microbiology and Immunology at the Uni- 
versity of California at San Francisco. 
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