title: The molecular mechanism of NELL2 movement and secretion in hippocampal progenitor HiB5 cells.
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.
authors.affiliation: Department of Physiology, Institute of Health Science, and Medical Research Center for Neural Dysfunction, Gyeongsang National University School of Medicine, Jinju, 660-290, Korea.
authors.forename: Chang Man
authors.initials: CM
authors.lastname: Ha
authors.forename: Eun Mi
authors.initials: EM
authors.lastname: Hwang
authors.forename: Eunju
authors.initials: E
authors.lastname: Kim
authors.forename: Da Yong
authors.initials: DY
authors.lastname: Lee
authors.forename: Sunghoe
authors.initials: S
authors.lastname: Chang
authors.forename: Byung Ju
authors.initials: BJ
authors.lastname: Lee
authors.forename: Seong-Geun
authors.initials: SG
authors.lastname: Hong
authors.forename: Jae-Yong
authors.initials: JY
authors.lastname: Park
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology* / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D021381:Protein Transport; D051381:Rats; D022161:Transport Vesicles / Q000378:metabolism
chemical_list: C491252:Nell2 protein, rat; D009419:Nerve Tissue Proteins