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The molecular mechanism of NELL2 movement and secretion in hippocampal progenitor HiB5 cells

Molecules and Cells volume 36, pages 527–533 (2013)Cite this article

Abstract

Neural epidermal growth factor-like protein-like 2 (NELL2) is a secreted glycoprotein that is predominantly expressed in the nervous system, but little is known about the intracellular movement and secretion mechanism of this protein. By monitoring the localization and movements of enhanced green fluorescent protein (EGFP)-labeled NELL2 in living cultured hippocampal neuroprogenitor HiB5 cells, we determined the subcellular localization of NELL2 and its intracellular movement and secretion mechanism. Cterminal EGFP-fused NELL2 showed a typical expression pattern of secreted proteins, especially with respect to its localization in the endoplasmic reticulum, Golgi apparatus, and punctate structures. Vesicles containing NELL2 exhibited bidirectional movement in HiB5 cells. The majority of the vesicles (70.1%) moved in an anterograde direction with an average velocity of 0.454 μm/s, whereas some vesicles (28.7%) showed retrograde movement with an average velocity of 0.302 μm/s. The movement patterns of NELL2 vesicles were dependent upon the presence of microtubules in HiB5 cells. Anterograde movement of NELL2 did not lead to a detectable accumulation of NELL2 in the peripheral region of the cell, indicating that it was secreted into the culture medium. We also showed that the N-terminal 29 amino acids of NELL2 were important for secretion of this protein. Taken together, these results strongly suggest that the N-terminal region of NELL2 determines both the pattern of its intracellular expression and transport of NELL2 vesicles by high-velocity movement. Therefore, NELL2 may affect the cellular activity of cells in a paracrine or autocrine manner.

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Affiliations

  1. Department of Physiology, Institute of Health Science, and Medical Research Center for Neural Dysfunction, Gyeongsang National University School of Medicine, Jinju, 660-290, Korea

    Chang Man Ha, Eun Mi Hwang, Eunju Kim, Seong-Geun Hong & Jae-Yong Park

  2. Convergence Brain Research Department, Korea Brain Research Institute (KBRI), Daegu, 700-010, Korea

    Chang Man Ha

  3. Center for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul, 136-791, Korea

    Eun Mi Hwang, Eunju Kim, Da Yong Lee & Jae-Yong Park

  4. Department of Biomedical Sciences, Neuroscience Research Institute, Biomembrane Plasticity Research Center, Seoul National University College of Medicine, Seoul, 110-799, Korea

    Sunghoe Chang

  5. Department of Biological Sciences, University of Ulsan, Ulsan, 680-749, Korea

    Byung Ju Lee

Authors
  1. Chang Man Ha
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  2. Eun Mi Hwang
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  3. Eunju Kim
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  4. Da Yong Lee
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  5. Sunghoe Chang
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  6. Byung Ju Lee
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  7. Seong-Geun Hong
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  8. Jae-Yong Park
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Correspondence to Jae-Yong Park.

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These authors contributed equally to this work.

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Ha, C.M., Hwang, E.M., Kim, E. et al. The molecular mechanism of NELL2 movement and secretion in hippocampal progenitor HiB5 cells. Mol Cells 36, 527–533 (2013). https://doi.org/10.1007/s10059-013-0216-5

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  • DOI: https://doi.org/10.1007/s10059-013-0216-5

Keywords

  • glycoprotein
  • intracellular movement
  • NELL2
  • secretion