Sp1 binds to the adhesion molecule on glia regulatory element that functions as a positive transcription regulatory element in astrocytes

We analyzed cis-acting elements regulating the expression of the gene encoding adhesion molecule on glia (AMOG) in primary cultured astrocytes from newborn rat cerebrum and cerebellum. The relative promoter activities among the series of 5- sequential deletion mutants are similar to those observed in B103 (rat neuroblastoma cell line) cells. The previously identified AMRE (AMOG regulatory element) of the GAGGCGGGG sequence functions as a positive regulatory element, not only in B103 cells, but also in astrocytes. Binding factors to the element were identified as Sp1 based on the following observations using nuclear extracts from the astrocytes and B103 cells: (1) The interaction of the factors with AMRE analyzed by DNase I footprinting and methylation interference analyses was similar to that of Sp1; (2) The binding of the factors to AMRE competed with an oligonucleotide containing the authentic Sp1 consensus sequence; (3) Sp1-specific antibody interfered with the formation of the AMRE gel retardation complexes. The functional implications of the factors in AMOG gene regulation are discussed. © 1993 Wiley-Liss, Inc.     

The neural cell adhesion molecule (NCAM) heparin binding domain binds to cell surface heparan sulfate proteoglycans.

The neural cell adhesion molecule (NCAM) has been strongly implicated in several aspects of neural development. NCAM mediated adhesion has been proposed to involve a homophilic interaction between NCAMs on adjacent cells. The heparin binding domain (HBD) is an amino acid sequence within NCAM and has been shown to be involved in NCAM mediated adhesion but the relationship of this domain to NCAM segments mediating homophilic adhesion has not been defined. In the present study, a synthetic peptide corresponding to the HBD has been used as a substrate to determine its role in NCAM mediated adhesion. A neural cell line expressing NCAM (B35) and its derived clone which does not express NCAM (B35 clone 3) adhered similarly to plates coated with HBD peptide. A polyclonal antiserum to NCAM inhibited B35 cell-HBD peptide adhesion by only 10%, a value not statistically different from inhibition caused by preimmune serum. Both these experiments suggested no direct NCAM-HBD interactions. To test whether the HBD peptide bound to cell surface heparan sulfate proteoglycans (HSPG), HSPG synthesis was inhibited using beta-D-xyloside. After treatment, B35 cell adhesion to the HBD peptide, but not to control substrates, was significantly decreased. B35 cell adhesion to the HBD peptide could be inhibited by 10(-7) M heparin but not chondroitin sulfate. Preincubation of the substrate (HBD peptide) with heparin caused dramatic reduction of B35 cell-HBD peptide adhesion whereas preincubation of B35 cells with heparin caused only modest reductions in cell-HBD adhesion. Furthermore, inhibition of HSPG sulfation with sodium chlorate also decreased the adhesion of B35 cells to the HBD peptide. These results strongly suggest that, within the assay system, the NCAM HBD does not participate in homophilic interactions but binds to cell surface heparan sulfate proteoglycan. This interaction potentially represents an important mechanism of NCAM adhesion and further supports the view that NCAM has multiple structurally independent binding sites.     

Oligodendrocyte cell adhesion molecules are related to neural cell adhesion molecule (N-CAM)

The glycoproteins responsible for calcium-dependent oligodendrocyte aggregation were purified and characterized. Using detergent extraction, lentil-lectin-Sepharose 4B affinity chromatography, and preparative gel electrophoresis, 3 proteins were purified to apparent homogeneity, with relative Mrs of 120,000, 140,000, and 180,000. The aggregation assay showed that all 3 proteins had the ability to block antibody-mediated inhibition of oligodendrocyte aggregation. The 120,000 protein was the most active of the three. Antisera were raised in rabbits to these 3 individual proteins. Western blot analyses showed that all three antisera recognized 120,000, 140,000, and 180,000 proteins, which indicated that the proteins were related. Western-blot analyses of cultured oligodendrocytes and purified rat myelin showed only the 120,000 protein. Immunoprecipitation of iodinated membrane proteins of cultured oligodendrocytes also indicated the presence of only the 120,000 Mr protein. Deglycosylation of the 120,000 protein by N-glycanase resulted in a 110,000 protein. The immunoblot pattern suggested some similarities between oligodendrocyte adhesion molecules and the neural cell adhesion molecule (N-CAM). Therefore, the 120,000, 140,000, and 180,000 Mr proteins were compared to N-CAM by Western-blot analysis, immunofluorescence staining, and by immunoprecipitation. The results suggest that oligodendrocytes contain a 120,000 membrane glycoprotein that is related to N-CAM.     

Polarized targeting of IgLON cell adhesion molecule OBCAM to dendrites in cultured neurons

Opioid-binding cell adhesion molecule (OBCAM) belongs to the immunoglobulin superfamily CAMs and shows a dendritically polarized distribution in hypothalamic magnocellular neurons. In the present study, the cellular localization of OBCAM was monitored in cultured cortical and hippocampal neurons to examine its polarized distribution. Double labeling immunofluorescence microscopy after fixation showed only faint OBCAM immunoreactivity in the neuronal somata during the early stages of culture, whereas the immunoreactivity was strong in MAP2-positive somata and dendrites of fully polarized neurons after longer culture. Moreover, the immunoreactivity for OBCAM showed a punctate pattern in the dendrites similar to the immunostaining pattern of synapsin I. High resolution revealed close apposition with only a partial overlap of synapsin I and OBCAM immunoreactivities, suggesting the synaptic localization of OBCAM to the dendrites. When the fully polarized neurons were reacted with anti-OBCAM antibody before fixation, OBCAM immunoreactivity became stronger on the dendritic surface than the somatic surface. Extracellular immunoreactivity was eliminated with phosphatidylinositol-specific phospholipase C and this immunoreactivity resisted extraction with the nonionic detergent Triton X-100 at 4 degrees C, indicating that OBCAM is attached to the rafts via a glycosylphosphatidyl inositol anchor. These results indicate that OBCAM is efficiently targeted to the dendritic surface of fully polarized cortical and hippocampal neurons. OBCAM is, hence, concluded to be a dendrite-associated CAM in cortical and hippocampal neurons as in hypothalamic magnocellular neurons.     

Basic fibroblast growth factor (bFGF) acts on both neurons and glia to mediate the neurotrophic effects of astrocytes on LHRH neurons in culture

Luteinizing hormone-releasing hormone (LHRH) neurons play a pivotal role in the neuroendocrine control of mammalian reproduction. Astrocytes were shown to be involved in the regulation of LHRH neuronal function, but little is known about the contribution of astroglial-derived factors in the regulation of LHRH neuron development. In order to gain insight into the mechanisms regulating the development of these cells, at morphological and biochemical levels we characterized the neurotrophic effects exerted by young astrocytes (maintained in culture for 8 days in vitro) and old astrocytes (maintained 26 days) on the differentiation, proliferation, and phenotypic expression of immortalized hypothalamic LHRH (GT(1-1)) neurons in vitro. Culturing GT(1-1) cells in the presence of young glia for different time intervals caused a marked acceleration in the acquisition of their neuronal phenotype. At all times examined, GT(1-1) cells cocultured with young glia exhibited a significantly greater extension of processes/cell, larger number of processes/cell and greater surface area of growth cones than GT(1-1) cells grown over nonglial adhesive substrates (polylysine). By contrast, when GT(1-1) neurons were cocultured with old glia, the length of neuronal processes and the growth cone surface area were significantly lower than in control GT(1-1) neurons cultured in the absence of glia. At 3 days in vitro (DIV), GT(1-1) neurons cocultured with young glia exhibited a 50% lower incorporation of [(3)H]thymidine than GT(1-1) neurons cultured without glia. By contrast, in the presence of old glia [(3)H]thymidine incorporation was significantly higher in cells cocultured with glia than in GT(1-1) neurons cultured alone. Localization of the proliferating cells by dual immunohistochemical staining revealed that the incorporation of bromodeoxiuridine (BrdU) was restricted to nuclei of GT(1-1) neurons when these were cocultured with young glia, but associated with both neurons and astrocytes in the presence of old glia. At the functional level, coculture of GT(1-1) neurons with young glia increased the spontaneous release of LHRH as compared to GT(1-1) neurons grown in the absence of glia. By contrast, in the presence of old glia LHRH release in the medium was significantly lower than in controls. Conditioned medium of young glia (ACM-Y) induced significant neurotrophic and functional effects on GT(1-1) cells, but these effects were 50% less potent than the coculture itself. Heat denaturation of ACM-Y totally abolished its neurotrophic and functional properties, indicating that they involved a peptide factor. Suppression of bFGF activity in ACM-Y reduced its neurotrophic activity by approximately 40%, but did not affect its LHRH release-promoting effects. By contrast, neutralization of endogenous bFGF activity in GT(1-1) neurons cocultured with young glia counteracted both neurotrophic and functional effects of young glia. Treatment of old glia with bFGF rescued its neurotrophic and functional effects on GT(1-1) cells. Moreover, the ACM of aged bFGF-treated old glia was the most powerful neurotrophic stimulus for GT(1-1) neurons. These results suggest that: 1) soluble peptidic factors, including bFGF, and mechanism(s) requiring coculture are responsible for the highly potent neurotrophic and functional effects of young glia; 2) the inhibitory effects of old glia on neurite outgrowth and LHRH release are mediated in part by soluble inhibitory molecules and in part by factors requiring coculture with old glia; 3) old glia may revert to a growth-supporting state when treated with bFGF and this functional shift involves a diffusible molecule with potent neurotrophic and functional effects on immortalized LHRH neurons. (c) 2000 Wiley-Liss, Inc.     

The effects of extracellular acidosis on neurons and glia in vitro

Cerebral lactic acid, a product of ischemic anaerobic glycolysis, may directly contribute to ischemic brain damage in vivo. In this study we evaluated the effects of extracellular acid exposure on 7-day-old cultures of embryonic rat forebrain. Mixed neuronal and glial cultures were exposed to either lactic or hydrochloric acid to compare the toxicities of relatively permeable and impermeable acids. Neurons were relatively resistant to extra-cellular HCl acidosis, often surviving 10-min exposures to pH 3.8. In the same cultures, immunochemically defined astrocytes survived 10-min HCl exposures to a maximum acidity of pH 4.2. Similarly, axonal bundles defasciculated in HCl-titrated media below pH 4.4, although their constituent fibers often survived pH 3.8. Cell death occurred at higher pH in cultures subjected to lactic acidosis than in those exposed to HCl. Over half of forebrain neurons and glia subjected for 10 min to lactic acidification failed to survive exposure to pH 4.9. Longer 1-h lactic acid incubations resulted in cell death below pH 5.2. The potent cytotoxicity of lactic acid may be a direct result of the relatively rapid transfer of its neutral protonated form across cell membranes. This process would rapidly deplete intracellular buffer stores, resulting in unchecked cytosolic acidification. Neuronal and glial death from extracellular acidosis may therefore be a function of both the degree and the rapidity of intracellular acidification.     

Immunocytochemical demonstration of neural cell adhesion molecule (NCAM) along the migration route of luteinizing hormone-releasing hormone (LHRH) neurons in mice.

Contact between the developing forebrain and the ingrowing central processes of the olfactory, vomeronasal and terminal nerves is preceded by a migration of neural cell adhesion molecule (NCAM)-immunoreactive cells from the epithelium of the olfactory pit and the formation of an NCAM-immunoreactive cellular aggregate in the mesenchyme between the olfactory pit and the forebrain. The axons of the olfactory, vomeronasal, and terminal nerves, also NCAM-immunoreactive, grow into the cellular aggregate, which as development proceeds, becomes continuous with the rostral tip of the forebrain. The lateral and more rostral part of the cellular aggregate receives the ingrowing axons of the olfactory nerves and becomes the olfactory nerve layer of the olfactory bulb. The medial, more caudal part receives the central processes of the vomeronasal and terminal nerves. The vomeronasal nerve ends in the accessory olfactory bulb. The central processes of the terminal nerve end in the medial forebrain. Luteinizing hormone-releasing hormone (LHRH)-immunoreactive neurons, like the vomeronasal and terminal nerves, originate from the medial part of the olfactory pit. These LHRH cells migrate into the brain along and within a scaffolding formed by the NCAM-immunoreactive axons of the vomeronasal and terminal nerves, and they are never seen independent of this NCAM scaffold as they cross the nasal lamina propria. The results suggest that: (1) NCAM is likely to be necessary for scaffold formation, and (2) the scaffold may be essential for the subsequent migration of LHRH neurons into the brain. Because they aggregate, migrating LHRH-immunoreactive neurons, on which we did not detect NCAM immunoreactivity, may interact via other cell adhesion molecules (CAM). Inasmuch as the interaction between the LHRH-immunoreactive neurons and the NCAM-immunoreactive scaffold is heterotypic, the possibility of a heterophilic (NCAM to other CAM) interaction is not ruled out. These findings focus our attention on the functional role of NCAM in this migratory system.     

Polysialic acid-neural cell adhesion molecule in brain plasticity: from synapses to integration of new neurons

Isoforms of the neuronal cell adhesion molecule (NCAM) carrying the linear homopolymer of alpha 2,8-linked sialic acid (polysialic acid, PSA) have emerged as particularly attractive candidates for promoting plasticity in the nervous system. The large negatively charged PSA chain of NCAM is postulated to be a spacer that reduces adhesion forces between cells allowing dynamic changes in membrane contacts. Accumulating evidence also suggests that PSA-NCAM-mediated interactions lead to activation of intracellular signaling cascades that are fundamental to the biological functions of the molecule. An important role of PSA-NCAM appears to be during development, when its expression level is high and where it contributes to the regulation of cell shape, growth or migration. However, PSA-NCAM does persist in adult brain structures such as the hippocampus that display a high degree of plasticity where it is involved in activity-induced synaptic plasticity. Recent advances in the field of PSA-NCAM research have not only consolidated the importance of this molecule in plasticity processes but also suggest a role for PSA-NCAM in the regulation of higher cognitive functions and psychiatric disorders. In this review, we discuss the role and mode of actions of PSA-NCAM in structural plasticity as well as its potential link to cognitive processes.     

An LRE (leucine-arginine-glutamate)-dependent mechanism for adhesion of neurons to S-laminin.

S-laminin is a homolog of laminin that is concentrated in the synaptic cleft of the neuromuscular junction. We previously showed that the tripeptide LRE is a crucial determinant for binding of ciliary motoneurons to recombinant s-laminin. Here, we describe a neuroblastoma-spinal neuron hybrid cell line, NSC-34, that binds to an LRE-containing s-laminin fragment and to a synthetic LRE-protein conjugate. NSC-34 cells exhibit several properties of motoneurons; other cell lines tested were not motoneuron-like and did not display LRE-dependent adhesion. We therefore used NSC-34 cells to characterize the LRE-dependent adhesion mechanism. Inhibition studies with a series of 20 tripeptide LRE analogs showed that the cells exhibit a high degree of selectivity for LRE, and suggested that ligand binding requires a combination of electrostatic and hydrophobic interactions. The effects of cations on LRE-dependent adhesion are unlike those of previously described adhesion molecules including the integrins, a family of receptors for extracellular matrix proteins, including laminin. Specifically, adhesion to LRE does not require divalent cations and is inhibited by Ca2+ (but not by Mg2+) in the physiological range. In contrast, adhesion of NSC-34 cells to laminin is LRE- and Ca2+ independent but Mg2+ dependent, and appears to be mediated by integrins. Additionally, experiments using mixed substrates demonstrated that LRE-protein conjugates inhibit neurite outgrowth promoted by laminin. Finally, we show that, under ionic conditions that minimize integrin-dependent adhesion, NSC-34 cells bind to s-laminin-rich basal laminae in tissue sections in an LRE-dependent manner. Together, these results suggest that LRE comprises a motoneuron-selective adhesion site that is accessible in native basal laminae and that acts to inhibit neurite outgrowth.     

Upregulation of intracellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 after unilateral nerve injury in the peripheral taste system

In the peripheral taste system, activated macrophages are recruited to both sides of the tongue after unilateral sectioning of the chorda tympani nerve (CT). Neural degeneration elicits macrophage entry in other systems by upregulating vascular adhesion molecules. We hypothesized that CT sectioning leads to a bilateral increase in intracellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 expression on lingual vessels. To test this hypothesis, rats were euthanized at time points from 6 hr to 7 days post-sectioning. Frozen sections of tongue were processed for immunohistochemical staining for ICAM-1 and VCAM-1. Tongue homogenates from additional rats were analyzed with ELISA. ICAM-1 expression increases first on the denervated side of the tongue at 24 hr post-section and then on the uninjured side at 48 hr post-section. ICAM-1 remains elevated through Day 7 post-sectioning on both sides of the tongue. Dietary sodium restriction, which prevents the macrophage response to nerve sectioning, had no effect on ICAM-1 levels. VCAM-1+ vessels are increased on the denervated side of the tongue at 24-48 hr post-section in control-fed rats. However, dietary sodium restriction prevents the increase. These results indicate that vascular adhesion molecules are differentially regulated by CT sectioning. We suggest that macrophage entry, migration, and modulation of taste function are downstream of dynamic expression of adhesion molecules.     

Localization of opioid-binding cell adhesion molecule (OBCAM) in adult rat brain

We investigated the tissue distribution and brain localization of opioid-binding cell adhesion molecule (OBCAM) in the adult rats by immunoblotting and immunohistochemistry using a monoclonal anti-OBCAM peptide antibody that is specific for OBCAM. OBCAM was preferentially expressed in the central nervous system (CNS) and at a very low level in the spleen. Within the brain, OBCAM was distributed in almost all the gray matter, but little or no immunoreactive OBCAM was found in the white matter. Morphologically, the distribution pattern of OBCAM immunoreactivity was very similar to that of synaptophysin, suggesting a role in the synaptic machinery.     

Developmental expression of opioid-binding cell adhesion molecule (OBCAM) in rat brain

Opioid-binding cell adhesion molecule (OBCAM), a neuron-specific protein, consists of three immunoglobulin (Ig)-like domains anchored to the membrane through a glycosylphosphatidylinositol (GPI)-tail. OBCAM has been presumed to play a role as a cell adhesion/recognition molecule, but its function has not been fully elucidated. We investigated the developmental expression of OBCAM in rat brain by using a monoclonal anti-OBCAM peptide antibody (OBC53). OBCAM was clearly detectable on embryonic day 16 (E16) as assessed by immunoblotting. The expression level increased by the second postnatal week and was maintained at a constant level until week 17. During the early developmental period OBCAM was found to be expressed on postmitotic neurons and to be strongly expressed in at the fiber tracts containing expanding axons, in contrast to the adult brain, in which OBCAM is principally expressed in the gray matter. These findings suggest that the function of OBCAM involves axonal outgrowth.     

The Adhesion Molecule on Glia (AMOG) Is Widely Expressed by Astrocytes in Developing and Adult Mouse Brain

Adhesion molecule on glia (AMOG) is a 45 - 50 kD cell surface glycoprotein structurally similar to the Na, K-ATPase beta-subunit and associated with the catalytic subunit of this enzyme. Previous immunofluorescence results had suggested that AMOG is transiently expressed on Bergmann glia during mouse cerebellar development, and antibody-inhibition results have implicated it in the migration of granule neurons. We report that, while AMOG mRNA is detected in Bergmann glia during the migratory period, this astrocyte derivative continues to express AMOG mRNA at similar levels in adult mice suggesting a functional role for AMOG in adulthood. Evidence from RNA and protein blot analyses that AMOG is present before birth, increasing about ten fold in adult mouse brain and cerebellum is also provided. RNA blot analysis of astrocyte-enriched cell populations and in situ hybridization results show that astrocytes synthesize AMOG mRNA in all regions of the developing and adult brain. In the adult, AMOG mRNA is more abundant in grey than white matter and, among grey matter regions, highest in cerebellar cortex. These results indicate a relationship between density of neuronal elements and AMOG expression. It is further speculated that AMOG is part of a Na,K-ATPase complex expressed preferentially by astrocytes in mouse brain.     

Expression of intercellular adhesion molecule 1 (ICAM-1) in Alzheimer's disease.

In this study, 13 clinically and pathologically diagnosed cases of Alzheimer's disease were analyzed for the presence of intercellular adhesion molecule 1 (ICAM-1), ICAM-2, lymphocyte function associated antigen-1 (LFA-1), HLA-DR, LN-1, and LN-2. ICAM-1 was observed primarily on neuritic plaques and cerebrovascular endothelium. ICAM-1 was also shown to be present in brain tissue derived from 14 normal cases; however, the degree of immunoreactivity was quantitatively less compared to Alzheimer cases and was largely restricted to cerebrovascular endothelium. LFA-1 was shown to be present on microglial cells and leukocytes. Consistent with the findings of previous reports, HLA-DR was found to be expressed on microglial cells. In this study we failed to demonstrate dual immunolocalization for ICAM-1 and LFA-1, ICAM-1 and HLA-DR, or ICAM-1 and LN-2. As microglial cells express both HLA-DR and LFA-1, they may serve to mediate antigen presentation functions by interacting with lymphocyte ICAM-1. Alternately, the expression of these immune-associated glycoproteins on glial cells may be epiphenomenal occurring secondary to some aspect of the disease process. Finally, the presence of ICAM-1 within neuritic plaques raises the question as to whether adhesion may play some role in the process of neurite outgrowth and neurodegeneration.     

Binding partners L1 cell adhesion molecule and the ezrin-radixin-moesin (ERM) proteins are involved in development and the regenerative response to injury of hippocampal and cortical neurons

Regeneration of the adult central nervous system may require recapitulation of developmental events and therefore involve the re-expression of developmentally significant proteins. We have investigated whether the L1 cell adhesion molecule, and its binding partner, the ezrin-radixin-moesin (ERM) proteins are involved in the neuronal regenerative response to injury. Hippocampal and cortical neurons were cultured in vitro on either an L1 substrate or poly-L-lysine, and ERM and other neuronal proteins were localized immunocytochemically both developmentally and following neurite transection of neurons maintained in long-term culture. Activated ERM was localized to growth cones up to 7 days in vitro but relatively mature cultures (21 days in vitro) were devoid of active ERM proteins. However, ERM proteins were localized to the growth cones of sprouting neuronal processes that formed several hours after neurite transection. In addition, the L1 substrate, relative to poly-L-lysine, resulted in significantly longer regenerative neurites, as well as larger growth cones with more filopodia. Furthermore, neurons derived from the cortex formed significantly longer post-injury neurite sprouts at 6 h post-injury than hippocampal derived neurons grown on both substrates. We have demonstrated that L1 and the ERM proteins are involved in the neuronal response to injury, and that neurons derived from the hippocampus and cortex may have different post-injury regenerative neurite sprouting abilities.     

The intimate relationship of gonadotropin-releasing hormone neurons with the polysialylated neural cell adhesion molecule revisited across development and adult plasticity

The neurohormone gonadotropin-releasing hormone (GnRH) is critical for all the aspects of reproductive life in vertebrates. GnRH is secreted by a small number of neurons dispersed within the preoptic-hypothalamic region. These neurons are derived from the embryonic olfactory pit. They then migrate along olfactory, vomeronasal and terminal nerves to their final destination. Classical approaches to study the regulation of GnRH secretion during the reproductive cycle have focused on the various neuronal inputs on GnRH neurons and their regulation by ovarian steroids. However, it is well known that steroids will change the microenvironment of neuronal networks and can induce plasticity and functional changes. In this review, we will focus on the intimate relationship of developing and adult GnRH neurons with the polysialylated form of neural cell adhesion molecule (PSA-NCAM), a major molecular actor in the morphogenesis and adult plasticity of the nervous system. We will first recapitulate the spatiotemporal relationship between PSA-NCAM and migrating GnRH neurons during embryogenesis of various vertebrate species and discuss its importance for GnRH neuron development as shown by various loss of function studies. In the adult, we will review the relationships between PSA-NCAM and GnRH neurons across various physiological states, and open the discussion to the use of new model systems that can help to unravel the function and mechanism of action of PSA-NCAM on GnRH neuronal network activity and GnRH release.     

The gp 120 glycoprotein of human immunodeficiency virus type 1 binds to sensory ganglion neurons

Using immunofluorescence microscopy we found that gp 120 binds to the surface of rat dorsal root ganglia neurons and human neuroblastoma cells but not to rat fibroblasts or glial cells. The binding of gp 120 to neurons was eliminated by pretreatment with trypsin, which removes cell-surface proteins, but not with chloroform: methanol, which removes glycolipids. As control, neuronal staining by antisulfatide antibodies was eliminated by pretreatment with chloroform: methanol but not with trypsin. The gp 120 binding to neurons was also inhibited by the mouse monoclonal antibody 01, which binds to galactocerebroside and cross-reactive glycoproteins. These studies suggest that the receptor for gp 120 on the surface of the dorsal root ganglia neurons is a glycoprotein. This interaction may mediate the effects of human immunodeficiency virus type 1 in sensory neuropathy.