Neurexophilins form a conserved family of neuropeptide-like glycoproteins.

Abstract

Neurexophilin was discovered as a neuronal glycoprotein that is copurified with neurexin Ialpha during affinity chromatography on immobilized alpha-latrotoxin (Petrenko et al., 1996). 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 Ialpha and IIIalpha but not neurexin Ibeta 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 alpha-neurexins. The structure and characteristics of neurexophilins indicate that they function as neuropeptides that may signal via alpha-neurexins.

• Authors: M Missler, T C Südhof
• Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 18 Issue 10 Pg. 3630-8 (May 15 1998) ISSN: 0270-6474 [Print] United States
• PMID: 9570794 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Glycoproteins
• Nerve Tissue Proteins
• Neuropeptides
• Spider Venoms
• neurexophilin
• alpha-latrotoxin
• Endopeptidases

Topics

• Animals
• COS Cells (enzymology)
• Cattle
• Cloning, Molecular
• Endopeptidases (metabolism)
• Gene Expression
• Glycoproteins (chemistry, genetics, metabolism)
• Humans
• Mice
• Molecular Sequence Data
• Multigene Family (genetics)
• Nerve Tissue Proteins (metabolism)
• Neurons (chemistry, drug effects, enzymology)
• Neuropeptides (chemistry, genetics, metabolism)
• PC12 Cells
• Protein Structure, Tertiary
• Rats
• Sequence Homology, Amino Acid
• Spider Venoms (pharmacology)