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Keywords = hippocalcin

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17 pages, 1020 KB  
Article
Hippocalcin Regulates NMDA Receptor Function and Neuronal Activity Through Elavl3 in Mouse Hippocampal Neural Precursor Cells
by Min-Jeong Kang, Sung Jun Jung, Hyeon Son, Joong-Soo Han and Shin-Young Park
Int. J. Mol. Sci. 2026, 27(5), 2439; https://doi.org/10.3390/ijms27052439 - 6 Mar 2026
Viewed by 333
Abstract
Hippocalcin (HPCA), a neuron-enriched calcium-binding protein, plays a critical role in brain function, but its role in neural precursor cells remains unclear. N-methyl-D-aspartate (NMDA) receptors are calcium-permeable glutamate receptors essential for neurodevelopment and synaptic plasticity, and their function has been implicated in neurological [...] Read more.
Hippocalcin (HPCA), a neuron-enriched calcium-binding protein, plays a critical role in brain function, but its role in neural precursor cells remains unclear. N-methyl-D-aspartate (NMDA) receptors are calcium-permeable glutamate receptors essential for neurodevelopment and synaptic plasticity, and their function has been implicated in neurological conditions. In this study, we investigated the role of HPCA in regulating NMDA receptor expression and function in mouse hippocampal neural precursor cells (mHNPCs). HPCA knockdown significantly reduced the expression of NMDA receptor-related genes, including Grin2C, Shank1, Serpine2, and selectively attenuated NMDA-induced calcium signaling. Transcriptomic analysis identified ELAV-like RNA-binding protein 3 (Elavl3), a neuron-enriched factor associated with neuronal activity, as a downstream candidate affected by HPCA knockdown. Consistently, Elavl3 suppression phenocopied HPCA deficiency, resulting in impaired NMDA receptor activity and reduced neuronal differentiation. Furthermore, hippocampal HPCA knockdown in vivo led to alterations in locomotor activity, contextual memory, and affective behaviors. Taken together, these findings demonstrate that HPCA supports NMDA receptor function and neuronal development, in part through Elavl3-associated pathways, and highlight HPCA as an important regulator of hippocampal function. Full article
(This article belongs to the Section Molecular Neurobiology)
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11 pages, 1231 KB  
Article
Calcium-Dependent Translocation of S100B Is Facilitated by Neurocalcin Delta
by Jingyi Zhang, Anuradha Krishnan, Hao Wu and Venkat Venkataraman
Molecules 2021, 26(1), 227; https://doi.org/10.3390/molecules26010227 - 5 Jan 2021
Cited by 3 | Viewed by 4316
Abstract
S100B is a calcium-binding protein that governs calcium-mediated responses in a variety of cells—especially neuronal and glial cells. It is also extensively investigated as a potential biomarker for several disease conditions, especially neurodegenerative ones. In order to establish S100B as a viable pharmaceutical [...] Read more.
S100B is a calcium-binding protein that governs calcium-mediated responses in a variety of cells—especially neuronal and glial cells. It is also extensively investigated as a potential biomarker for several disease conditions, especially neurodegenerative ones. In order to establish S100B as a viable pharmaceutical target, it is critical to understand its mechanistic role in signaling pathways and its interacting partners. In this report, we provide evidence to support a calcium-regulated interaction between S100B and the neuronal calcium sensor protein, neurocalcin delta both in vitro and in living cells. Membrane overlay assays were used to test the interaction between purified proteins in vitro and bimolecular fluorescence complementation assays, for interactions in living cells. Added calcium is essential for interaction in vitro; however, in living cells, calcium elevation causes translocation of the NCALD-S100B complex to the membrane-rich, perinuclear trans-Golgi network in COS7 cells, suggesting that the response is independent of specialized structures/molecules found in neuronal/glial cells. Similar results are also observed with hippocalcin, a closely related paralog; however, the interaction appears less robust in vitro. The N-terminal region of NCALD and HPCA appear to be critical for interaction with S100B based on in vitro experiments. The possible physiological significance of this interaction is discussed. Full article
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