Complementary expression and heterophilic interactions between IgLON family members neurotrimin and LAMP.
Neurotrimin (Ntm) and the limbic system-associated membrane protein (LAMP) are members of the IgLON (LAMP, OBCAM, Ntm) family of glycorylphosphatidylinositol anchored neural cell adhesion molecules. We previously reported that LAMP and Ntm promote adhesion and neurite outgrowth via a homophilic mechanism, suggesting that these proteins promote the formation of specific neuronal circuits by homophilic interactions. In this report, we have further characterized the expression and binding specificity of Ntm. Using a newly generated monoclonal antibody to Ntm, we demonstrated that this protein is largely expressed in a complementary pattern to that of LAMP in the nervous system, with co-expression at a few sites. Ntm is expressed at high levels in sensory-motor cortex and, of particular note, is transiently expressed in neurons of cortical barrel fields and corresponding thalamic "barreloids." Binding of a recombinant, soluble form of Ntm to CHO cells expressing either Ntm or LAMP demonstrates that Ntm and LAMP interact both homophilically and heterophilically. In contrast to conventional growth-promoting activity of Ig superfamily members, LAMP strongly inhibits the outgrowth of Ntm-expressing dorsal root ganglion (DRG) neurons in a heterophilic manner. These anatomical and functional data support the concept that homophilic and heterophilic interactions between IgLON family members are likely to play a role in the specification of neuronal projections via growth promoting and inhibiting effects, respectively.
Gil
Orlando D
OD
Department of Cell Biology, New York University School of Medicine, 550 First Avenue, New York, New York 10016, USA.
Zhang
Li
L
Chen
Suzanne
S
Ren
Y Q
YQ
Pimenta
Aurea
A
Zanazzi
George
G
Hillman
Dean
D
Levitt
Pat
P
Salzer
James L
JL
D000818:Animals; D000911:Antibodies, Monoclonal; D016466:CHO Cells; D015816:Cell Adhesion Molecules, Neuronal / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D006224:Cricetinae; D058851:GPI-Linked Proteins; D005727:Ganglia, Spinal / Q000166:cytology / Q000254:growth & development; D008032:Limbic System / Q000166:cytology* / Q000254:growth & development; D051379:Mice; D008807:Mice, Inbred BALB C; D009046:Motor Neurons / Q000378:metabolism / Q000648:ultrastructure; D019006:Neural Cell Adhesion Molecules / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D016501:Neurites / Q000378:metabolism*; D009475:Neurons, Afferent / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D013003:Somatosensory Cortex / Q000166:cytology / Q000254:growth & development; D014162:Transfection
D000911:Antibodies, Monoclonal; D015816:Cell Adhesion Molecules, Neuronal; D058851:GPI-Linked Proteins; D019006:Neural Cell Adhesion Molecules; C095362:limbic system-associated membrane protein; C092530:neurotrimin