leagues isolated cDNA clones encoding this glyco- 
protein. The deduced protein sequence of TAG-1 
indicates that it is a member of the immunoglobu- 
lin gene family, closely related in structure to other 
axonal glycoproteins implicated in neuronal recog- 
nition, in particular Fll, LI, and N-CAM (neural 
cell adhesion molecule). TAG-1 possesses a large 
extracellular region that contains six immunoglob- 
ulin-like domains and four domains that are homol- 
ogous to type III sequences found in the extracellu- 
lar matrix protein fibronectin. In addition, TAG-1 
contains an Arg-Gly-Asp (RGD) sequence that has 
been identified in many cell surface and extracellu- 
lar matrix proteins that interact with the integrin 
family of receptors. These findings suggest that 
TAG-1 has multiple distinct binding domains. TAG- 
1 does not possess a transmembrane domain but 
has a hydrophobic carboxyl-terminal region that is 
indicative of membrane anchoring via a glycosyl 
phosphatidylinositol linkage. In support of this, 
biochemical studies have shown that TAG-1 is re- 
leased from the surface of neurons by phos- 
pholipase C. The isolation of full-length TAG-1 
cDNA clones will permit a detailed analysis of the 
structure and function of this axonal glycoprotein. 
III. Isolation and Functional Properties of Neuro- 
transmitter Receptors. 
Molecular studies of the serotonin receptor gene 
family have continued, in collaboration with Dr. 
Richard Axel (HHMI, Columbia University). Many of 
the actions of serotonin within the central nervous 
system, including the control of affective and per- 
ceptual states, are mediated by the 5HT2 receptor 
subtype. A cDNA encoding a rat brain 5HT2 recep- 
tor has been isolated by virtue of its homology with 
the 5HTlc receptor. The 5HT2 receptor is a new 
PUBLICATIONS 
member of the family of G protein-linked receptors 
that span the lipid bilayer seven times. Overall se- 
quence identity between the 5HT2 and 5HTlc re- 
ceptors is 49%, but identity within the transmem- 
brane domains is 80%. Expression of functional 5HT2 
receptors in Xenopus oocytes and transfected 
mouse fibroblasts indicates that, like the 5HTlc re- 
ceptor, this receptor activates phospholipase C sig- 
naling pathways and elevates intracellular Ca^"*". 
These structural and functional similarities indicate 
that serotonin receptors derive from at least two 
gene families. The 5HTlc and 5HT2 receptors de- 
fine one gene family, whereas the 5HTla receptor 
has evolved from a distinct adrenergic receptor 
lineage. 
The functional consequences of activating a 
brain-specific neurotransmitter receptor, the sero- 
tonin 5HTlc receptor, in the unnatural environ- 
ment of a fibroblast have also been examined. In- 
troduction of functional 5HTlc receptors into NIH 
3T3 cells results, at high frequency, in the genera- 
tion of transformed foci. Moreover, the generation 
and maintenance of transformed foci requires con- 
tinued activation of the serotonin receptor. The in- 
jection of cells derived from transformed foci into 
nude mice results in the generation of tumors. 
These findings indicate that the serotonin 5HTlc 
receptor functions as a proto-oncogene when ex- 
pressed in NIH 3T3 fibroblasts. Thus the distinction 
between a neurotransmitter receptor, a growth fac- 
tor receptor, and an oncogene may depend criti- 
cally on the cellular environment. 
Dr. Jessell is also Associate Professor of Biochem- 
istry and Molecular Biophysics and Member of the 
Center for Neurobiology and Behavior at the Co- 
lumbia University College of Physicians and Sur- 
geons. 
Books and Chapters of Books 
Hynes, M.A., Dodd, J., and Jessell, TM. 1989. Carbohydrate recognition, cell interactions and vertebrate neu- 
ral development. \r\ Neurobiology of Glycoconjugates (Margolis, R.U., and Margolis, R.K., Eds.). New York: 
Plenum, pp 337-365. 
Jessell, T.M. , and Dodd, J. 1989- Functional chemistry of primary afferent neurons. In Textbook of Pain (Wall, 
PD., and Melzack, R., Eds.). Edinburgh: Churchill Livingstone, ed 2, pp 82-99. 
Articles 
Chou, D.K.H., Dodd, J., Jessell, T.M. , Costello, C.E., and Jungalwala, KB. 1989. Identification of a-galactose 
(a-fucose)-asiolo-Gj^j glycolipid expressed by subsets of rat dorsal root ganglion neurons. / Biol Chem 
264:3409-3415. 
Continued 
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