The limbic system-associated membrane protein is an Ig superfamily member that mediates selective neuronal growth and axon targeting

Pimenta, Aurea F.; Zhukareva, Victoria; Barbe, Mary F.; Reinoso, Blesilda S.; Grimley, Christopher; Henzel, William J.; Fischer, Itzhak; Levitt, Pat

doi:10.1016/0896-6273(95)90034-9

Cited by 160 publications

(158 citation statements)

References 53 publications

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“…To generate the targeting vector, a mouse 129/ReJ genomic library constructed in the λ FIX II vector (provided by Dr John Pintar, UMDNJ-RWJMS, Piscataway, NJ) was screened using probes derived from the rat Lsamp cDNA [41]. Among the Lsamp genomic clones isolated and characterized, the mLsamp-λ-11a clone was selected for containing a 13.2 kb insert, including the partial nucleotide sequence of the first intron, exon 2 and ∼4.0 kb of intron 2.…”

Section: Lsamp Targetingmentioning

confidence: 99%

“…Poly(A) + RNA (1 μg) was separated on a 1.5% agarose-formaldehyde gel, transferred to a nylon membrane (Nytran SuperCharge, Schleicher and Schuel, Keene, NH), UV cross-linked, and hybridized overnight under stringent conditions with 32 P-labeled cRNA probes. Antisense probes were transcribed in vitro using T7 RNA polymerase from rat Lsamp cDNA template [41] linearized with MscI (nt 464−1238). GeneBank accession number for the rat Lsamp nucleotide sequence is U31554.…”

Section: Northern Blot Analysismentioning

confidence: 99%

“…The protein exhibits 99% homology between rodent and human [38] and there is a close correlation between Lsamp mRNA and protein distribution patterns in rat [29,39,44,54], monkey [5,6], and human [42,43]. Experimental manipulations of LAMP in vitro result in altered axon targeting and neurite growth [13,24,31,41,56]. In the analysis of different rat substrains, Nelovkov and colleagues correlated lower expression of Lsamp mRNA in the amygdala and hippocampus with decreased anxiety and increased exploration [35,36].…”

Section: Introductionmentioning

confidence: 99%

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Genetic Deletion of Lsamp Causes Exaggerated Behavioral Activation in Novel Environments

Catania

Pimenta

Levitt

2007

Behavioural Brain Research

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The limbic system-associated membrane protein (LAMP) is a GPI-anchored cell adhesion molecule expressed heavily in limbic and limbic-associated regions of the developing and adult brain. Experimental studies show that LAMP promotes the growth of limbic neurons and guides the projections of limbic fibers. In order to examine the functional consequences of disrupting limbic circuit assembly, we generated a mouse line in which the Lsamp gene encoding LAMP was deleted. Basic neuroanatomical organization and sensory and motor development are normal in Lsamp −/− mice. The most profound change in behavior in both male and female Lsamp −/− mice is a heightened reactivity to novelty exhibited in several behavioral tests. Lsamp −/− mice display hyperactivity in a novel arena and both sexes habituate to the same activity levels as their wildtype littermates, but at different rates. In the elevated plus maze, Lsamp −/− mice exhibit increased total arm entries, with a bias towards the open arms; they spend more time in the open arms and have a substantial increase in the amount of risk assessment in unprotected areas of the maze. In the y-maze, Lsamp −/− mice exhibit characteristic hyperactivity and a decreased level of spontaneous alternation during the period when their novelty-induced hyperactivity is at its peak. We hypothesize that Lsamp −/− mice may not simply exhibit a decrease in anxiety, but may have a heightened, and possibly maladaptive, response to novel environmental stressors. Genetic deletion of Lsamp may thus cause circumscribed changes in the fine connectivity of specific circuits that underlie these behaviors.

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Section: Lsamp Targetingmentioning

confidence: 99%

Section: Northern Blot Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Genetic Deletion of Lsamp Causes Exaggerated Behavioral Activation in Novel Environments

Catania

Pimenta

Levitt

2007

Behavioural Brain Research

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“…14 Among the IgCAMs, the IgLON family comprises LAMP, OB-CAM, Ntm, and Kilon. 9,10,17,18 In rats Ntm is detectable from E15 prenatally, rises gradually, and peaks during the first and second postnatal week. Thereafter, Ntm message levels gradually decline to about half maximal levels in the adult.…”

Section: Discussionmentioning

confidence: 99%

“…[5][6][7] IgCAMs are the key proteins that regulate neurite outgrowth and the development of specific projections. 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.…”

Section: Introductionmentioning

confidence: 99%

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

Grijalva

Marcillo

et al. 2005

Spinal Cord

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Study design: Neurotrimin (Ntm) is a member of the family of neural cell adhesion molecules. Its expression pattern suggests that Ntm promotes axonal fasciculation, guides nerve fibers to specific targets and stabilizes synapses as it accumulates coincident with synaptogenesis. Strong labeling of Ntm was observed in motor and sensory areas of the postnatal rat cortex. It is not known whether Ntm is present in adult human spinal cord (SC). In the present study, a monoclonal antibody specific for Ntm (1B1), is applied to the first study of the expression of Ntm in normal and injured adult human SC. Objective: (1) To investigate the expression pattern of Ntm in adult normal human SC, and (2) to observe the changes of Ntm expression after SC injury and compare the differences between normal and injured adult human SC. Methods: Human SC tissue was obtained from necropsies of patients with (n ¼ 5) and without (n ¼ 4) SC injury. The 1B1 Ntm monoclonal antibody was used for immunohistochemical staining on paraffin embedded sections with an ABC kit. Results: (1) In total, 12 slides were analyzed for each group from both cervical and thoracic levels. Motor neurons and Clarke's neurons and glial-like cells were mild to moderately positive in all uninjured SC specimens. (2) In injured SC, no staining was observed in the injury epicenter between two and three levels proximally and distally, but was detected five levels away. (3) In patients older than 67 years of age, Ntm-positive inclusions were present in the white matter of the SC with or without injury. (4) Some meningeal cells were strongly Ntm-positive, especially in the uninjured human SC. Conclusion: Ntm is expressed by motor and Clarke's neurons and glial cells in uninjured human SC. The downregulation of Ntm in the injured SC suggests that its expression is regulated by afferent input.

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Expression of the mRNAs encoding the limbic system‐associated membrane protein (LAMP): I. Adult rat brain

1996

Self Cite

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The search for molecular markers common to neural structures that are functionally related has become an attractive strategy for neurobiologists interested in identifying mechanisms involved in the formation of patterned connections. One such molecule is the limbic system-associated membrane protein (LAMP), a 64-68 kDa glycoprotein that is expressed in the soma and dendrites of subpopulations of adult neurons in the brain that are functionally associated with classic limbic structures. Such patterned molecular specificity is established prenatally; LAMP is detected during development on the surface of neurons, axonal membranes and pathfinding growth cones. This molecule has now been cloned (lamp) and has been shown to be highly conserved in rat and human. It is a new immunoglobulin superfamily member that has three Ig domains and a glycosyl-phosphatidylinositol (GPI) anchor to the cell membrane. In this study, the distribution of the lamp transcript in the adult rat brain was determined by using in situ hybridization. Generally, the distribution of lamp corresponds well with that of the LAMP protein. Within the cerebral cortex, the transcript is more abundant in areas that are associated with learning/memory and viscerosensory tasks. It is less abundant in somatic sensory and motor areas. The lamp transcript is also ubiquitous in the basal forebrain, amygdala, and preopticohypothalamic areas. In short, the lamp transcript is expressed heavily in areas of the forebrain and diencephalon that have been classically considered limbic and sparsely or moderately in nonlimbic midbrain and hindbrain regions. Correlative analysis of the connectivity patterns of the regions that express greater amounts of the transcript is consistent with a stronger limbic-associated function relative to the regions expressing less lamp. These quantitative differences may be significant in determining the function of LAMP in the adult brain.

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The limbic system-associated membrane protein is an Ig superfamily member that mediates selective neuronal growth and axon targeting

Cited by 160 publications

References 53 publications

Genetic Deletion of Lsamp Causes Exaggerated Behavioral Activation in Novel Environments

Genetic Deletion of Lsamp Causes Exaggerated Behavioral Activation in Novel Environments

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

Expression of the mRNAs encoding the limbic system‐associated membrane protein (LAMP): I. Adult rat brain

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