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

Authors
Ha, Chang ManHwang, Eun MiKim, EunjuLee, Da YongChang, SunghoeLee, Byung JuHong, Seong-GeunPark, Jae-Yong
Issue Date
Dec-2013
Publisher
KOREAN SOC MOLECULAR & CELLULAR BIOLOGY
Keywords
glycoprotein; intracellular movement; NELL2; secretion
Citation
MOLECULES AND CELLS, v.36, no.6, pp.527 - 533
Journal Title
MOLECULES AND CELLS
Volume
36
Number
6
Start Page
527
End Page
533
URI
http://scholarworks.bwise.kr/kbri/handle/2023.sw.kbri/896
DOI
10.1007/s10059-013-0216-5
ISSN
1016-8478
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 mu m/s, whereas some vesicles (28.7%) showed retrograde movement with an average velocity of 0.302 mu m/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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