Back to Search Start Over

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

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

Authors :
Debalina Datta
Namrata Singh
Laxmikant G. Gadhe
Samir K. Maji
Ambuja Navalkar
A. Paul
Pradeep Kadu
Santosh Kumar
Reeba S. Jacob
Shantibhushan Senapati
Chinmai Pindi
Shinjinee Sengupta
Soumik Ray
Debdeep Chatterjee
Praful S. Singru
Publication Year :
2021
Publisher :
Cold Spring Harbor Laboratory, 2021.

Abstract

Synergistic-aggregation and cross-seeding by two different amyloid proteins/peptides are well evident in various neurological disorders. However, this phenomenon is not well studied in functional amyloid aggregation. Here, we show Prolactin (PRL) is associated with lactation in mammals and neuropeptide galanin (GAL), which are co-stored in the lactotrophs facilitates the synergic aggregation in the absence of secretory granules helper molecules glycosaminoglycans (GAGS). Interestingly, although each partner possesses homotypic seeding ability, a unidirectional cross-seeding of GAL aggregation can be mediated by PRL seeds. The specificity of co-aggregation by PRL and GAL along with unidirectional cross-seeding suggests tight regulation of functional amyloid formation during co-storage of these hormones in secretory granule biogenesis of female rat lactotrophs. Further mixed fibrils release the constituent functional hormone much faster than the corresponding individual amyloid formed in presence of GAGs, suggesting that co-aggregation of functionally distant hormones might have evolved for efficient storage, synergistic and rapid release of both hormones upon stimulation. The co-aggregation and cross seeding by two different hormones of completely different structures and sequences (PRL and GAL) suggest a novel mechanism of heterologous amyloid formation both in disease and functional amyloids.

Details

Database :
OpenAIRE
Accession number :
edsair.doi...........1f9d8c4671e24ce90515514c99c47ebb
Full Text :
https://doi.org/10.1101/2021.08.31.458467