CDNA CLONING AND STRUCTURAL-ANALYSIS OF THE HUMAN LIMBIC-SYSTEM-ASSOCIATED MEMBRANE-PROTEIN (LAMP)

The limbic-system-associated membrane protein (LAMP) is a 64-68-kDa ne uronal surface glycoprotein distributed in cortical and subcortical re gions of the limbic system. The human LAMP gene was cloned by RT-PCR u sing human cerebral cortex mRNA and oligodeoxyribonucleotide (oligo) p rimers derived from the rat lamp cDNA sequence. The human and rat LAMP cDNAs showed 94% identity at the nucleotide (nt) level, and the encod ed 338-amino-acid (aa) polypeptides shared 99% sequence identity. All the important features of LAMP were conserved: (i) the deduced aa sequ ence reflecting a glycosyl-phosphatidylinositol (GPI)-anchor, (ii) eig ht putative N-linked glycosylation sites, and (iii) conserved pairs of Cys forming three internal repeats characteristic of the immunoglobul in superfamily (IgSF). Northern blot analysis indicated the presence o f two mRNA transcripts in the human brain of a size identical to those identified in adult rat brain. These data indicate that LAMP is a hig hly conserved new member of the IgSF which, together with the opioid-b inding cell adhesion molecule (OBCAM) and neurotrimin, comprises a new subfamily that has been designated as IgLONs. With a unique distribut ion in limbic structures, LAMP may play an important role in limbic sy stem development and function, as suggested by previous in vitro and i n vivo functional studies.