Co-aggregation and secondary nucleation in the life cycle of human prolactin/galanin functional amyloids

  1. Debdeep Chatterjee
  2. Reeba S Jacob
  3. Soumik Ray
  4. Ambuja Navalkar
  5. Namrata Singh
  6. Shinjinee Sengupta
  7. Laxmikant Gadhe
  8. Pradeep Kadu
  9. Debalina Datta
  10. Ajoy Paul
  11. Sakunthala Arunima
  12. Surabhi Mehra
  13. Chinmai Pindi
  14. Santosh Kumar
  15. Praful Singru
  16. Sanjib Senapati
  17. Samir K Maji  Is a corresponding author
  1. Indian Institute of Technology Bombay, India
  2. Indian Institute of Technology Madras, India
  3. National Institute of Science Education and Research, India

Abstract

Synergistic-aggregation and cross-seeding by two different proteins/peptides in the amyloid aggregation are well evident in various neurological disorders including Alzheimer’s disease. Here, we show co-storage of human Prolactin (PRL), which is associated with lactation in mammals, and neuropeptide galanin (GAL) as functional amyloids in secretory granules (SGs) of the female rat. Using a wide variety of biophysical studies, we show that irrespective of the difference in sequence and structure, both hormones facilitate their synergic aggregation to amyloid fibrils. Although each hormone possesses homotypic seeding ability, a unidirectional cross-seeding of GAL aggregation by PRL seeds and the inability of cross seeding by mixed fibrils suggest tight regulation of functional amyloid formation by these hormones for their efficient storage in SGs. Further, the faster release of functional hormones from mixed fibrils compared to the corresponding individual amyloid, suggests a novel mechanism of heterologous amyloid formation in functional amyloids of SGs in the pituitary.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting file; Source Data files have been provided for main Figures 1-5 and Supplementary figures and tables.

Article and author information

Author details

  1. Debdeep Chatterjee

    Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, India
    Competing interests
    The authors declare that no competing interests exist.
  2. Reeba S Jacob

    Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, India
    Competing interests
    The authors declare that no competing interests exist.
  3. Soumik Ray

    Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, India
    Competing interests
    The authors declare that no competing interests exist.
  4. Ambuja Navalkar

    Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, India
    Competing interests
    The authors declare that no competing interests exist.
  5. Namrata Singh

    Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, India
    Competing interests
    The authors declare that no competing interests exist.
  6. Shinjinee Sengupta

    Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, India
    Competing interests
    The authors declare that no competing interests exist.
  7. Laxmikant Gadhe

    Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, India
    Competing interests
    The authors declare that no competing interests exist.
  8. Pradeep Kadu

    Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, India
    Competing interests
    The authors declare that no competing interests exist.
  9. Debalina Datta

    Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, India
    Competing interests
    The authors declare that no competing interests exist.
  10. Ajoy Paul

    Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, India
    Competing interests
    The authors declare that no competing interests exist.
  11. Sakunthala Arunima

    Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, India
    Competing interests
    The authors declare that no competing interests exist.
  12. Surabhi Mehra

    Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, India
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1777-673X
  13. Chinmai Pindi

    Department of Biotechnology, Indian Institute of Technology Madras, Chennai, India
    Competing interests
    The authors declare that no competing interests exist.
  14. Santosh Kumar

    School of Biological Sciences, National Institute of Science Education and Research, Bhubaneswar, India
    Competing interests
    The authors declare that no competing interests exist.
  15. Praful Singru

    School of Biological Sciences, National Institute of Science Education and Research, Bhubaneswar, India
    Competing interests
    The authors declare that no competing interests exist.
  16. Sanjib Senapati

    Department of Biotechnology, Indian Institute of Technology Madras, Chennai, India
    Competing interests
    The authors declare that no competing interests exist.
  17. Samir K Maji

    Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, India
    For correspondence
    samirmaji@iitb.ac.in
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9110-1565

Funding

Department of Biotechnology, Ministry of Science and Technology, India (BT/PR9797/NNT/28/774/2014)

  • Samir K Maji

Department of Biotechnology, Ministry of Science and Technology, India (BT/HRD/35/01/03/2020)

  • Samir K Maji

Department of Science and Technology, Ministry of Science and Technology, India (CRG/2019/001133)

  • Samir K Maji

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Adult, female, Sprague-Dawley rats taken for this study were maintained under the standard environmental conditions and Institutional Animal Ethical Committee (IAEC) at NISER, Bhubaneswar, India approved the experimental protocols. (Protocol Numbers: NISER/SBS/AH-210 and NISER/SBS/AH-212).

Copyright

© 2022, Chatterjee et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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https://doi.org/10.7554/eLife.73835