Complementary expression and heterophilic interactions between igLON family members neurotrimin and LAMP

Abstract

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.

Branched Sialylated <i>N</i>-glycans Are Accumulated in Brain Synaptosomes and Interact with Siglec-H

“…Neurotrimin and LAMP are members of the IgLON family of immunoglobulin domain-containing glycosylphosphatidylinositolanchored cell adhesion molecules. These proteins are expressed in neurons and function in the development and stabilization of synapses (Gil et al, 1998(Gil et al, , 2002Hashimoto et al, 2009;McNamee et al, 2002;Sanz et al, 2015). Our results suggest that branched sialylated A2G´2F is expressed in synapses on carrier proteins, like calreticulin, neurotrimin and LAMP, and this N-glycan may contribute to synapse formation, maintenance and pruning.…”

“…However, there are few reports of the localization of calreticulin in the brain, where neurotrimin and LAMP are known to be synaptic proteins contributing to synapse formation (Gil et al, 1998(Gil et al, , 2002Hashimoto et al, 2009;McNamee et al, 2002;Sanz et al, 2015). To examine calreticulin localization in the brain, western blot analysis of subcellular fractionated samples of 12w mouse brain was performed.…”

Expression of neurotrimin in the normal and injured adult human spinal cord

“…Previous reports indicate that Ntm is not expressed at significant levels by cultured astrocytes or Schwann cells based on biochemistry and PCR analysis. 10,12 Meningeal cells have been shown to produce neuronal factors, [21][22][23] which may inhibit axonal regrowth. However, Lakatos et al 24 recently reported that adding meningeal cells to …”

“…Among the IgCAMs, limbic system-associated membrane protein (LAMP), opioid-binding cell adhesion molecule (OBCAM), and neurotrimin (Ntm) are founding members of the IgLON family, [8][9][10] which also includes Kilon/neurotractin, 11 they represent the earliest and most abundant glycosylphosphatidylinositol (GPI)-anchored proteins expressed by neurons. 12 Ntm is expressed at high levels in several developing projection systems of the rat: neurons of the thalamus, subplate lower cortical laminae in the forebrain and in the pontine nucleus, cerebellar granule cells, and Purkinje cells in the hindbrain. Ntm is also expressed at high levels in the olfactory bulb, neural retina, dorsal root ganglia, spinal cord (SC), and in a graded distribution in the basal ganglia and hippocampus.…”

IgLONs form heterodimeric complexes on forebrain neurons

“…28 The expression of individual IgLONs has been investigated extensively and although each has its own distinct expression pattern there are many regions of overlap. 20,[29][30][31][32][33][34] …”