Neuronal growth regulator 1 (NEGR1) promotes the synaptic targeting of glutamic acid decarboxylase 65 (GAD65).

Neuronal growth regulator 1 (NEGR1) is a synaptic plasma membrane localized cell adhesion molecule implicated in a wide spectrum of psychiatric disorders. By RNAseq analysis of the transcriptomic changes in the brain of NEGR1-deficient mice, we found that NEGR1 deficiency affects the expression of the Gad2 gene. We show that glutamic acid decarboxylase 65 (GAD65), the Gad2 - encoded enzyme synthesizing the inhibitory neurotransmitter GABA on synaptic vesicles, accumulates non-synaptically in brains of NEGR1-deficient mice.

Cell Adhesion Molecules as Modulators of the Epidermal Growth Factor Receptor.

Cell adhesion molecules (CAMs) are cell surface glycoproteins mediating interactions of cells with other cells and the extracellular matrix. By mediating the adhesion and modulating activity of other plasma membrane proteins, CAMs are involved in regulating a multitude of cellular processes, including growth, proliferation, migration, and survival of cells. In this review, we present evidence showing that various CAMs interact with the epidermal growth factor receptor (EGFR), a receptor tyrosine kinase inducing pro-proliferative and anti-apoptotic intracellular signaling in response to binding to several soluble ligands, including the epidermal growth factor.

Deficiency in the neural cell adhesion molecule 2 (NCAM2) reduces axonal levels of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), affects axonal organization in the hippocampus, and leads to behavioral deficits.

The neural cell adhesion molecule 2 (NCAM2) regulates axonal organization in the central nervous system via mechanisms that have remained poorly understood. We now show that NCAM2 increases axonal levels of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), a protease that regulates axonal guidance. In brains of NCAM2-deficient mice, BACE1 levels are reduced in hippocampal mossy fiber projections, and the infrapyramidal bundle of these projections is shortened.

The BACE1-generated C-terminal fragment of the neural cell adhesion molecule 2 (NCAM2) promotes BACE1 targeting to Rab11-positive endosomes.

Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), also known as β-secretase, is an aspartic protease. The sorting of this enzyme into Rab11-positive recycling endosomes regulates the BACE1-mediated cleavage of its substrates, however, the mechanisms underlying this targeting remain poorly understood. The neural cell adhesion molecule 2 (NCAM2) is a substrate of BACE1.

Amyloid precursor protein (APP) and amyloid β (Aβ) interact with cell adhesion molecules: Implications in Alzheimer's disease and normal physiology.

Alzheimer's disease (AD) is an incurable neurodegenerative disorder in which dysfunction and loss of synapses and neurons lead to cognitive impairment and death. Accumulation and aggregation of neurotoxic amyloid-β (Aβ) peptides generated amyloidogenic processing of amyloid precursor protein (APP) is considered to play a central role in the disease etiology. APP interacts with cell adhesion molecules, which influence the normal physiological functions of APP, its amyloidogenic and non-amyloidogenic processing, and formation of Aβ aggregates.

RNA polyadenylation patterns in the human transcriptome.

The eukaryotic transcriptome undergoes various post-transcriptional modifications which assists gene expression. Polyadenylation is a molecular process occurring at the 3'-end of the RNA molecule which involves the poly(A) polymerase attaching adenine monophosphate molecules in a chain-like fashion to assemble a poly(A) tail. Multiple RNA isoforms are produced with differing 3'-UTR and exonic compositions through alternative polyadenylation (APA) which enhances the diversification of alternatively spliced mRNA transcripts.

Cell Adhesion Molecules and Protein Synthesis Regulation in Neurons.

Cell adhesion molecules (CAMs) mediate interactions of neurons with the extracellular environment by forming adhesive bonds with CAMs on adjacent membranes or binding to proteins of the extracellular matrix. Binding of CAMs to their extracellular ligands results in the activation of intracellular signaling cascades, leading to changes in neuronal structure and the molecular composition and function of neuronal contacts. Ultimately, many of these changes depend on the synthesis of new proteins.

Neural glycomics: the sweet side of nervous system functions.

The success of investigations on the structure and function of the genome (genomics) has been paralleled by an equally awesome progress in the analysis of protein structure and function (proteomics). We propose that the investigation of carbohydrate structures that go beyond a cell's metabolism is a rapidly developing frontier in our expanding knowledge on the structure and function of carbohydrates (glycomics). No other functional system appears to be suited as well as the nervous system to study the functions of glycans, which had been originally characterized outside the nervous system.

Trafficking and Activity of Glutamate and GABA Receptors: Regulation by Cell Adhesion Molecules.

The efficient targeting of ionotropic receptors to postsynaptic sites is essential for the function of chemical excitatory and inhibitory synapses, constituting the majority of synapses in the brain. A growing body of evidence indicates that cell adhesion molecules (CAMs), which accumulate at synapses at the earliest stages of synaptogenesis, are critical for this process. A diverse variety of CAMs assemble into complexes with glutamate and GABA receptors and regulate the targeting of these receptors to the cell surface and synapses.

NCAM regulates temporal specification of neural progenitor cells via profilin2 during corticogenesis.

The development of cerebral cortex requires spatially and temporally orchestrated proliferation, migration, and differentiation of neural progenitor cells (NPCs). The molecular mechanisms underlying cortical development are, however, not fully understood. The neural cell adhesion molecule (NCAM) has been suggested to play a role in corticogenesis.

Early transcriptome changes in response to chemical long-term potentiation induced via activation of synaptic NMDA receptors in mouse hippocampal neurons.

Long term potentiation (LTP) is a form of synaptic plasticity. In the present study LTP was induced via activation of synaptic NMDA receptors in primary hippocampal neuron cultures from neonate mice and RNA was isolated for RNA sequencing at 20 min following LTP induction. RNA sequencing and differential expression testing was performed to determine the identity and abundance of protein-coding and non-coding RNAs in control and LTP induced neuron cultures.

Cell Adhesion Molecule Close Homolog of L1 (CHL1) Guides the Regrowth of Regenerating Motor Axons and Regulates Synaptic Coverage of Motor Neurons.

The close homolog of L1 (CHL1) is a cell adhesion molecule involved in regulation of neuronal differentiation and survival, neurite outgrowth and axon guidance during development. In the mature nervous system, CHL1 regulates synaptic activity and plasticity. The aim of the present study was to evaluate the influence of CHL1 on peripheral nerve regeneration after trauma.

Neural Cell Adhesion Molecule 2 (NCAM2)-Induced c-Src-Dependent Propagation of Submembrane Ca2+ Spikes Along Dendrites Inhibits Synapse Maturation.

The neural cell adhesion molecule 2 (NCAM2) is encoded by a gene on chromosome 21 in humans. NCAM2 accumulates in synapses, but its role in regulation of synapse formation remains poorly understood. We demonstrate that an increase in NCAM2 levels results in increased instability of dendritic protrusions and reduced conversion of protrusions to dendritic spines in mouse cortical neurons.

Glycosylphosphatidylinositol-Anchored Immunoglobulin Superfamily Cell Adhesion Molecules and Their Role in Neuronal Development and Synapse Regulation.

Immunoglobulin superfamily (IgSF) cell adhesion molecules (CAMs) are cell surface glycoproteins that not only mediate interactions between neurons but also between neurons and other cells in the nervous system. While typical IgSF CAMs are transmembrane molecules, this superfamily also includes CAMs, which do not possess transmembrane and intracellular domains and are instead attached to the plasma membrane via a glycosylphosphatidylinositol (GPI) anchor. In this review, we focus on the role GPI-anchored IgSF CAMs have as signal transducers and ligands in neurons, and discuss their functions in regulation of neuronal development, synapse formation, synaptic plasticity, learning, and behavior.

Replicable Expansion and Differentiation of Neural Precursors from Adult Canine Skin.

Repopulation of brain circuits by neural precursors is a potential therapeutic strategy for neurodegenerative disorders; however, choice of cell is critical. Previously, we introduced a two-step culture system that generates a high yield of neural precursors from small samples of adult canine skin. Here, we probe their gene and protein expression profiles in comparison with dermal fibroblasts and brain-derived neural stem cells and characterize their neuronal potential.

Neural Cell Adhesion Molecules of the Immunoglobulin Superfamily Regulate Synapse Formation, Maintenance, and Function.

Immunoglobulin superfamily adhesion molecules are among the most abundant proteins in vertebrate and invertebrate nervous systems. Prominent family members are the neural cell adhesion molecules NCAM and L1, which were the first to be shown to be essential not only in development but also in synaptic function and as key regulators of synapse formation, synaptic activity, plasticity, and synaptic vesicle recycling at distinct developmental and activity stages. In addition to interacting with each other, adhesion molecules interact with ion channels and cytokine and neurotransmitter receptors.

Transcriptional regulation of long-term potentiation.

Long-term potentiation (LTP), the persistent strengthening of synapses following high levels of stimulation, is a form of synaptic plasticity that has been studied extensively as a possible mechanism for learning and memory formation. The strengthening of the synapse that occurs during LTP requires cascades of complex molecular processes and the coordinated remodeling of pre-synaptic and post-synaptic neurons. Despite over four decades of research, our understanding of the transcriptional mechanisms and molecular processes underlying LTP remains incomplete.

KCa1.1, a calcium-activated potassium channel subunit alpha 1, is targeted by miR-17-5p and modulates cell migration in malignant pleural mesothelioma.

Background: Malignant pleural mesothelioma (MPM) is an aggressive, locally invasive, cancer elicited by asbestos exposure and almost invariably a fatal diagnosis. To date, we are one of the leading laboratory that compared microRNA expression profiles in MPM and normal mesothelium samples in order to identify dysregulated microRNAs with functional roles in mesothelioma. We interrogated a significant collection of MPM tumors and normal pleural samples in our biobank in search for novel therapeutic targets.

Synaptic Cell Adhesion Molecules in Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative brain disorder associated with the loss of synapses between neurons in the brain. Synaptic cell adhesion molecules are cell surface glycoproteins which are expressed at the synaptic plasma membranes of neurons. These proteins play key roles in formation and maintenance of synapses and regulation of synaptic plasticity.

Reciprocal Interactions between Cell Adhesion Molecules of the Immunoglobulin Superfamily and the Cytoskeleton in Neurons.

Cell adhesion molecules of the immunoglobulin superfamily (IgSF) including the neural cell adhesion molecule (NCAM) and members of the L1 family of neuronal cell adhesion molecules play important functions in the developing nervous system by regulating formation, growth and branching of neurites, and establishment of the synaptic contacts between neurons. In the mature brain, members of IgSF regulate synapse composition, function, and plasticity required for learning and memory. The intracellular domains of IgSF cell adhesion molecules interact with the components of the cytoskeleton including the submembrane actin-spectrin meshwork, actin microfilaments, and microtubules.

Aβ-dependent reduction of NCAM2-mediated synaptic adhesion contributes to synapse loss in Alzheimer's disease.

Alzheimer's disease (AD) is characterized by synapse loss due to mechanisms that remain poorly understood. We show that the neural cell adhesion molecule 2 (NCAM2) is enriched in synapses in the human hippocampus. This enrichment is abolished in the hippocampus of AD patients and in brains of mice overexpressing the human amyloid-β (Aβ) precursor protein carrying the pathogenic Swedish mutation.

Intracellular transport and cell surface delivery of the neural cell adhesion molecule (NCAM).

The neural cell adhesion molecule (NCAM) regulates differentiation and functioning of neurons by accumulating at the cell surface where it mediates the interactions of neurons with the extracellular environment. NCAM also induces a number of intracellular signaling cascades, which coordinate interactions at the cell surface with intracellular processes including changes in gene expression, transport and cytoskeleton remodeling. Since NCAM functions at the cell surface, its transport and delivery to the cell surface play a critical role.