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International Journal of Hematology

, Volume 108, Issue 2, pp 130–138 | Cite as

The localization of α-synuclein in the process of differentiation of human erythroid cells

  • Katsuya Araki
  • Kotomi Sugawara
  • Eri H. Hayakawa
  • Kumi Ubukawa
  • Isuzu Kobayashi
  • Hideki Wakui
  • Naoto Takahashi
  • Kenichi Sawada
  • Hideki Mochizuki
  • Wataru Nunomura
Original Article

Abstract

Although the neuronal protein α-synuclein (α-syn) is thought to play a central role in the pathogenesis of Parkinson’s disease (PD), its physiological function remains unknown. It is known that α-syn is also abundantly expressed in erythrocytes. However, its role in erythrocytes is also unknown. In the present study, we investigated the localization of α-syn in human erythroblasts and erythrocytes. Protein expression of α-syn increased during terminal differentiation of erythroblasts (from day 7 to day 13), whereas its mRNA level peaked at day 11. α-syn was detected in the nucleus, and was also seen in the cytoplasm and at the plasma membrane after day 11. In erythroblasts undergoing nucleus extrusion (day 13), α-syn was detected at the periphery of the nucleus. Interestingly, we found that recombinant α-syn binds to trypsinized inside-out vesicles of erythrocytes and phosphatidylserine (PS) liposomes. The dissociation constants for binding to PS/phosphatidylcholine (PC) liposomes of N-terminally acetylated (NAc) α-syn was lower than that of non NAc α-syn. This suggests that N-terminal acetylation plays a significant functional role. The results of the present study collectively suggest that α-syn is involved in the enucleation of erythroblasts and the stabilization of erythroid membranes.

Keywords

α-Synuclein Human erythroblasts Human erythrocytes Phosphatidylserine 

Notes

Acknowledgements

The authors thank Dr. Philippe Gascard (University of California) for critical evaluation and editing of the manuscript. The authors are grateful to Ms. Etsuko Kobayashi (Akita University) for her valuable technical assistance with immunocytochemistry. The authors are grateful to Mr. Tatsufumi Goto (Akita University), Mr. Ken Asanuma (Akita University) and Mr. Junsuke Yamashita (Akita University) for their valuable technical assistance with real time PCR. The authors thank Dr. Masahiko Hatakeyama (CLEA Japan Inc.) for generating the mouse monoclonal antibody to human α-syn (16E2).

Funding

This work was supported by JSPS KAKENHI Grants 15K09448 (WN), 15K09516 (HW), 15K19540 (KU), 15K14339 (KA), 26461414 (NT), 26461439 (KSa), and 26293210 (HM) and grants from Translational Research Network Program (HM), the SENSHIN Medical Research Foundation and the Idiopathic Disorders of Hematopoietic Organs Research Committee of the Ministry of Health, Labour and Welfare of Japan. This work was also supported in part by a private donation from Dr. Ken Satoh (Satoh Naika Clinic).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

12185_2018_2457_MOESM1_ESM.docx (2.1 mb)
Supplementary material 1 (DOCX 2152 KB)

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Copyright information

© The Japanese Society of Hematology 2018

Authors and Affiliations

  1. 1.Department of Neurology, Graduate School of MedicineOsaka UniversitySuitaJapan
  2. 2.Department of Hematology, Nephrology, and Rheumatology, Master Course of Graduate School of MedicineAkita UniversityAkitaJapan
  3. 3.Division of Medical Zoology, Department of Infection and ImmunityJichi Medical UniversityShimotsukeJapan
  4. 4.Department of Hematology, Nephrology, and Rheumatology, Graduate School of MedicineAkita UniversityAkitaJapan
  5. 5.Department of Life Science, Graduate School of Engineering ScienceAkita UniversityAkitaJapan
  6. 6.Akita UniversityAkitaJapan
  7. 7.Research Center for Engineering Science, Graduate School of Engineering ScienceAkita UniversityAkitaJapan

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