The Journal of Neuroscience, May 15, 1998, 18(10):3630-3638
Neurexophilins Form a Conserved Family of Neuropeptide-Like
Glycoproteins
Markus
Missler and
Thomas C.
Südhof
Howard Hughes Medical Institute and Department of Molecular
Genetics, The University of Texas Southwestern Medical School, Dallas,
Texas 75235
Neurexophilin was discovered as a neuronal glycoprotein that is
copurified with neurexin I
during affinity chromatography on
immobilized -latrotoxin (). We have now investigated how neurexophilin interacts with neurexins, whether it is
post-translationally processed by site-specific cleavage similar to
neuropeptides, and whether related neuropeptide-like proteins are
expressed in brain. Our data show that mammalian brains contain four
genes for neurexophilins the products of which share a common structure
composed of five domains: an N-terminal signal peptide, a variable
N-terminal domain, a highly conserved central domain that is
N-glycosylated, a short linker region, and a conserved C-terminal
domain that is cysteine-rich. When expressed in pheochromocytoma (PC12)
cells with a replication-deficient adenovirus, neurexophilin 1 was
rapidly N-glycosylated and then slowly processed to a smaller mature
form, probably by endoproteolytic cleavage. Similar expression
experiments in other neuron-like cells and in fibroblastic cells
revealed that N-glycosylation of neurexophilin 1 occurred in all cell
types tested, whereas proteolytic processing was observed only in
neuron-like cells. Finally, only recombinant neurexin I and III
but not neurexin I
interacted with neurexophilin 1 and were
preferentially bound to the processed mature form of neurexophilin.
Together our data demonstrate that neurexophilins form a family of
related glycoproteins that are proteolytically processed after
synthesis and bind to -neurexins. The structure and characteristics
of neurexophilins indicate that they function as neuropeptides that may
signal via -neurexins.
Key words:
neurexins; -latrotoxin; synapse; gene duplication; proteolytic processing; neuropeptides; adenovirus expression
Copyright © 1998 Society for Neuroscience 0270-6474/98/18103630-09$05.00/0
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