engleski

Neuroplastin in the human brain

The cell adhesion glycoprotein neuroplastin (Np, NPTN) has stepped into the spotlight when its genetic variants were associated with the cortical thickness and levels of intellectual abilities in adolescents. Immunohistochemical studies of the human hippocampus revealed that neuroplastin expression delineates the trisynaptic pathway important for episodic memory formation, whereas data from rodent experiments showed that Np antibodies inhibit maintenance of hippocampal long-term potentiation (LTP). Furthermore, genetically-induced deletion of brain-specific neuroplastin isoform causes retrograde amnesia in mice. Structurally, Np is a heavily glycosylated transmembrane protein found in two splice isoforms, neuroplastin-65 (Np65) and neuroplastin- 55 (Np55). Np55 is detected in wide range of tissues and has been found in the human breast and lung cancer. However, an adhesive function and a potential role of Np55 in altered cellular proliferation have not been clarified. Np65 is involved in neurite outgrowth, LTP regulation, maintenance of hippocampal CA1 synaptic plasticity, and associative memory formation. It interacts with GABAA receptor subunits in hippocampal inhibitory synapses and regulates ratio of excitatory and inhibitory synapses. Interestingly, data from functional proteomics determined neuroplastin as an essential auxiliary subunit of plasma membrane Ca2+ ATPase (PMCA), which is one of the key regulators of Ca2+ signaling and membrane transport. Here we summarize our immunohistochemical data on neuroplastin expression in the human brain during development and its specific immunoreactivity pattern in cell-containing layers of the adult human hippocampus. In addition, we present the transcriptomic expression pattern of neuroplastin and four PMCA isoforms (NPTN, ATP2B1, ATP2B2, ATP2B3, and ATP2B4) in the hippocampus, cerebellum and neocortex from 10 post-conception weeks (PCW) to 82-year of age, analyzed using a previously published microarray database. The high expression level and similar expression pattern of all analyzed genes indicate functional interplay of neuroplastin and PMCA which could underlie specific neuronal functions, e.g. LTP, that rely on ion homeostasis.

neuroplastin ; PMCA ; human brain ; memory ; calcium homeostasis

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