記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SOC NEUROSCIENCE  

Damage-induced neuronal endopeptidase (DINE)/endothelin-converting enzyme-like 1 (ECEL1) is a membrane-bound metalloprotease, which we originally identified as a nerve regeneration-associated molecule. Abundant expression of DINE is observed in regenerating neurons, as well as in developing spinal motor neurons. In line with this, DINE-deficient (DINE KO) embryos fail to arborize phrenic motor nerves in the diaphragm and to form proper neuromuscular junctions (NMJ), which lead to death shortly after birth. However, it is unclear whether protease activity of DINE is involved in motor nerve terminal arborization and how DINE participates in the process. To address these issues, we performed an in vivo rescue experiment in which three types of motor-neuron specific DINE transgenic mice were crossed with DINE KO mice. The DINE KO mice, which overexpressed wild-type DINE in motor neurons, succeeded in rescuing the aberrant nerve terminal arborization and lethality after birth, while those overexpressing two types of protease domain-mutated DINE failed. Further histochemical analysis showed abnormal behavior of immature Schwann cells along the DINE-deficient axons. Coculture experiments of motor neurons and Schwann cells ensured that the protease domain of neuronal DINE was required for proper alignment of immature Schwann cells along the axon. These findings suggest that protease activity of DINE is crucial for intramuscular innervation of motor nerves and subsequent NMJ formation, as well as proper control of interactions between axons and immature Schwann cells.

DOI： 10.1523/JNEUROSCI.3811-15.2016

Web of Science

PubMed

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: PAP-III is a secretory protein expressed in injured nerves. Results: Extracellular PAP-III formed fibrillar structures upon proteolytic N-terminal processing, interacted with neuronal surfaces, and enhanced neurite extension. Conclusion: Fibrillar PAP-III formed around injury sites may serve as a scaffold for the growth of regenerating axons. Significance: Clarifying fibrillar PAP-III functions would provide a novel strategy for nerve regeneration. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.

DOI： 10.1074/jbc.M112.395301

Scopus

PubMed

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

The regenerating gene/regenerating islet-derived (Reg) family is a group of small secretory proteins. Within this family, Reg type-III (Reg-III) consists of: Reg-III alpha, -beta, -gamma, and -delta. To elucidate the physiological relevance of Reg-III, we examined the localization and ontogeny of Reg-III beta and Reg-III gamma in mice at different time points spanning from embryonic day 13.5 to 7 weeks old, using in situ hybridization and immunohistochemistry. Our results showed that Reg-III beta was expressed in specific subsets of primary sensory neurons and motor neurons, and that expression was transient during the embryonic and perinatal periods. Reg-III beta expression was also observed in absorptive epithelial cells of the intestine. In contrast, Reg-III gamma expression was mainly observed in epithelial cells of the airways and intestine, but not in the nervous system, and expression levels showed a gradually increasing pattern along with development. In the airways Reg-III gamma was expressed in goblet and Clara-like cells, whereas in the intestine Reg-III gamma was expressed in the absorptive epithelial cells and Paneth cells, and was found to be expressed in development before these organs had been exposed to the outside world. The present findings imply that Reg-III beta and Reg-III gamma expression is regulated along divergent pathways. Furthermore, we also suggest that expression of Reg-III gamma in the airway and intestinal epithelia may occur to protect these organs from exposure to antigens or other factors (e.g., microbes) in the outer world, whereas the transient expression of Reg-III beta in the nervous system may be associated with the development of the peripheral nervous system including such processes as myelination. J. Comp. Neurol., 2012;520:479494. (C) 2011 Wiley Periodicals, Inc.

DOI： 10.1002/cne.22705

Web of Science

PubMed

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACADEMIC PRESS INC ELSEVIER SCIENCE  

Under continuous stress (CS) in rats, melanotrophs, the predominant cell-type in the intermediate lobe (IL) of the pituitary, are hyperactivated to secrete alpha-melanocyte-stimulating hormone and thereafter degenerate. Although these phenomena are drastic, the molecular mechanisms underlying the cellular changes are mostly unknown. In this study, we focused on the pancreatitis-associated protein (PAP) family members of the secretory lectins and characterized their expression in the IL of CS model rats because we had identified two members of this family as up-regulated genes in our previous microarray analysis. RT-PCR and histological studies demonstrated that prominent PAP-I and PAP-II expression was induced in melanotrophs in the early stages of CS, while another family member, PAP-III, was not expressed. We further examined the regulatory mechanisms of PAP-I and PAP-II expression and revealed that both were induced by the decreased dopamine levels in the IL under CS. Because the PAP family members are implicated in cell survival and proliferation, PAP-land PAP-II secreted from melanotrophs may function to sustain homeostasis of the IL under CS conditions in an autocrine or a paracrine manner. (C) 2011 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.bbrc.2011.02.064

Web of Science

PubMed

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER IRELAND LTD  

DOI： 10.1016/j.neures.2010.07.1119

Web of Science

記述言語：英語   会議種別：口頭発表（一般）  

記述言語：英語   会議種別：口頭発表（一般）  

記述言語：英語   会議種別：口頭発表（一般）  

記述言語：英語   会議種別：口頭発表（一般）  

記述言語：日本語   会議種別：口頭発表（一般）  

記述言語：英語   会議種別：ポスター発表  

開催地：千葉  

記述言語：日本語   会議種別：ポスター発表  

開催地：名古屋