Regulation of multiple tip formation by caffeine in cellular slime molds

Jaiswal, P., Singh, S. P. , Aiyar, P., Akkali, R. and Baskar, R. (2012) Regulation of multiple tip formation by caffeine in cellular slime molds. BMC Developmental Biology, 12, 26. (doi: 10.1186/1471-213x-12-26) (PMID:22928977) (PMCID:PMC3488011)

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Background: The multicellular slug in Dictyostelium has a single tip that acts as an organising centre patterning the rest of the slug. High adenosine levels at the tip are believed to be responsible for this tip dominance and the adenosine antagonist, caffeine overrides this dominance promoting multiple tip formation. Results: Caffeine induced multiple tip effect is conserved in all the Dictyostelids tested. Two key components of cAMP relay namely, cAMP phosphodiesterase (Pde4) and adenyl cyclase-A (AcaA) levels get reduced during secondary tip formation in Dictyostelium discoideum. Pharmacological inhibition of cAMP phosphodiesterase also resulted in multiple tips. Caffeine reduces cAMP levels by 16.4, 2.34, 4.71 and 6.30 folds, respectively in D. discoideum, D. aureostipes, D. minutum and Polysphondylium pallidum. We propose that altered cAMP levels, perturbed cAMP gradient and impaired signalling may be the critical factors for the origin of multiple tips in other Dictyostelids as well. In the presence of caffeine, slug cell movement gets impaired and restricted. The cell type specific markers, ecmA (prestalk) and pspA (prespore) cells are not equally contributing during additional tip formation. During additional tip emergence, prespore cells transdifferentiate to compensate the loss of prestalk cells. Conclusion: Caffeine decreases adenyl cyclase–A (AcaA) levels and as a consequence low cAMP is synthesised altering the gradient. Further if cAMP phosphodiesterase (Pde4) levels go down in the presence of caffeine, the cAMP gradient breaks down. When there is no cAMP gradient, directional movement is inhibited and might favour re-differentiation of prespore to prestalk cells.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Singh, Dr Shashi
Authors: Jaiswal, P., Singh, S. P., Aiyar, P., Akkali, R., and Baskar, R.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:BMC Developmental Biology
Publisher:BioMed Central
ISSN (Online):1471-213X
Copyright Holders:Copyright © 2012 Jaiswal et al.
First Published:First published in BMC Developmental Biology 12: 26
Publisher Policy:Reproduced under a Creative Commons License

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