NPTN

Official Full Name

neuroplastin

Organism

Homo sapiens

GeneID

27020

Background

This gene encodes a type I transmembrane protein belonging to the Ig superfamily. The protein is believed to be involved in cell-cell interactions or cell-substrate interactions. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2009]

Synonyms

GP55; GP65; SDR1; np55; np65; SDFR1;

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Detailed Information

Neuroplastin (Nptn) is a cell adhesion molecule that is rich in synaptic membranes and belongs to the immunoglobulin superfamily. There are two isomers of np65 and np55. np65 is brain-specific and np55 is systemic. Neuroplastin can play a role in long-term enhancement, synaptic plasticity, and promotion of neurite outgrowth. It may be related to learning, memory, and emotion.

Nptn Figure 1. A strategy for preventing melanoma lung-tropic metastasis. (Tomonobu, N., et al. 2020)

Nptn and schizophrenia

Nptn belongs to the immunoglobulin superfamily of cell adhesion molecules and is mainly located on the synaptic membrane. Among them, np65 is a unique glycoprotein in the brain and is mainly present in neurons of the forebrain, while np55 exists in various regions and other tissues in the brain. In different organisms, np65 and np55 are highly glycosylated and present many different glycosylation forms. Part of the fucosylation of np65 is related to long-term memory formation and long term potentiation (LTP). The immunoreactivity of np65 in post-synaptic density area (PSD) is significantly increased, indicating that np65 can be transferred to PSD in order to maintain neuronal activity. And using np65 antibody or np65- Fc recombinant protein can inhibit LTP, which indicates that the maintenance of np65 and LTP is related to synaptic plasticity.

Gangliosides are present on the cell membrane and play an important role in the development and maintenance of central and peripheral nervous system functions. The expression of mRNA of Nptn in ganglioside-deficient mice was significantly increased, the expression of np55 protein was also significantly increased, and the np immune response in the CA1, CA3 region and the dentate gyrus molecular cell layer was significantly reduced. Because gangliosides and Nptn play important roles in synaptic transmission, synaptic plasticity, and neurite growth. Changes in the proportion of ganglioside composition types in the brain will affect the expression and distribution of Nptn. Therefore, Nptn and ganglioside interact.

The relationship between Nptn and emotional abnormalities

Schizophrenia is a common psychiatric disorder. It can be concluded that schizophrenia is genetically susceptible through the clustering of families and the incidence of twins. NPTN, located on chromosome 15q22, is a risk factor for schizophrenia and is thought to be related to visual attention in patients. A study of 200 schizophrenia patients in Japan showed that there is a single nucleotide polymorphism in the 5 'end promoter of NPTN, which exists in 4 forms. Among them, del-G-G is overexpressed in patients with schizophrenia, while TG-G appears more frequently in normal people than in patients. The presence of T-G-G in the promoter can reduce the transcription of NPTN, thereby interfering with the excessive affinity binding between np molecules, so T-G-T can be used as a protective factor for schizophrenia.

Nptn and breast cancer

Neuroplastin expression was found during screening of tumor cell antigens in the B-cell proliferative area of breast cancer patients' lymph nodes. In subsequent studies, it was found that the expression was mainly np55 with relative molecular masses of 45 000 and 55 000. Among patients with tumors with a positive neuroplastin expression, distant tumor metastasis was found in 50% of patients and lymph node metastasis was found in 20%, indicating that the expression of Neuroplastin increases the probability of tumor cell metastasis. Therefore, np55 may be used as a tumor marker for breast cancer, thus becoming an indicator of breast cancer screening and treatment effect detection. Studies have shown that the expression of Fibroblast Growth Factor Receptor-1 (FGFR1) is increased in 8% to 15% of breast cancer patients, which suggests that np55 activation of FGFR is an important pathophysiological process in some types of breast cancer patients.

References:

Tomonobu, N., Kinoshita, R., & Sakaguchi, M. (2020). S100 Soil Sensor Receptors and Molecular Targeting Therapy Against Them in Cancer Metastasis. Translational oncology, 13(4), 100753. Advance online publication.
Gong, D., Chi, X., Ren, K., Huang, G., Zhou, G., Yan, N., Lei, J., & Zhou, Q. (2018). Structure of the human plasma membrane Ca2+-ATPase 1 in complex with its obligatory subunit neuroplastin. Nature communications, 9(1), 3623.

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