NCAM2 promotes targeting of APP from the cell surface to BACE1-containing recycling endosomes.

Convergence of amyloid precursor protein (APP) and β-site APP cleaving enzyme 1 (BACE1) in endosomes initiates the production of amyloid-β (Aβ) peptides that accumulate in brains of Alzheimer's disease patients. APP and BACE1 are segregated in neurons, and mechanisms triggering their convergence have remained poorly understood, limiting therapeutic attempts to reduce Aβ production. Neural cell adhesion molecule 2 (NCAM2) is a cell surface localized protein, which increases Aβ levels via mechanisms that are not known.

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.

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.

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.

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.

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.