Co-aggregation and secondary nucleation in the life cycle of human prolactin/galanin functional amyloids
- Indian Institute of Technology Bombay, India
- Indian Institute of Technology Madras, India
- 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
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).
Reviewing Editor
- Mishaela R Rubin, Columbia University Medical Center, United States
Publication history
- Preprint posted: September 1, 2021 (view preprint)
- Received: September 13, 2021
- Accepted: March 3, 2022
- Accepted Manuscript published: March 8, 2022 (version 1)
- Version of Record published: April 8, 2022 (version 2)
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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Co-aggregation and secondary nucleation in the life cycle of human prolactin/galanin functional amyloids
eLife 11:e73835.
https://doi.org/10.7554/eLife.73835
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