title: N-terminal cleaved pancreatitis-associated protein-III (PAP-III) serves as a scaffold for neurites and promotes neurite outgrowth.
abstract: Pancreatitis-associated protein (PAP)-III, also known as regenerating gene/regenerating islet-derived (Reg)-IIIγ, is a small secretory protein whose expression is substantially induced in injured nerves. Here, we found that PAP-III protein underwent proteolytic N-terminal processing by trypsin-like protease(s) in injured sciatic nerves after axotomy. In vitro studies demonstrated that the N terminus-truncated PAP-III (ΔN-PAP-III) polymerized into a filament with a relatively uniform diameter of 10-20 nm, and the filaments formed higher order structures in a Na(+) concentration-dependent manner. When the ΔN-PAP-III fibers were added to the culture media, the ΔN-PAP-III fibers were tightly attached to neurites and somata of primary cortical neurons in vitro. In contrast, little association with glial cells was observed. When dense matrices of ΔN-PAP-III fibers were sheeted on a culture dish, neurites preferentially adhered to the fibers, and neurite extension was enhanced. This neurite outgrowth activity was significantly suppressed by preincubation with antibodies against PAP-III. These results imply that the released PAP-III might be cleaved and forms ΔN-PAP-III fibers at the nerve injury sites. Consequently, these resulting fibers would provide regenerating axons with a platform for extension.
authors: Department of Functional Anatomy and Neuroscience, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors: Hiroyuki
authors: H
authors: Konishi
authors: Sakiko
authors: S
authors: Matsumoto
authors: Kazuhiko
authors: K
authors: Namikawa
authors: Hiroshi
authors: H
authors: Kiyama
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D001369:Axons / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009416:Nerve Regeneration / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D016501:Neurites / Q000378:metabolism*; D000073718:Pancreatitis-Associated Proteins; D059748:Proteolysis; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000293:injuries / Q000378:metabolism; D012964:Sodium / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D037181:Lectins, C-Type; D009419:Nerve Tissue Proteins; D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human; C000612144:Reg3b protein, rat; C000612145:Reg3g protein, rat; D012964:Sodium