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Encystation stimuli sensing mediated by adenylate cyclase AC2-dependent cAMP signaling in Giardia

Protozoan parasites use cAMP signaling to precisely regulate the place and time of developmental differentiation, yet it is unclear how this signaling is initiated. Encystation of the intestinal parasite Giardia lamblia can be activated by multiple stimuli, which we hypothesize result in a common ph...

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Autores principales: Shih, Han-Wei, Alas, Germain C.M., Paredez, Alexander R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Journal Experts 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10168462/
https://www.ncbi.nlm.nih.gov/pubmed/37162830
http://dx.doi.org/10.21203/rs.3.rs-2818450/v1
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author Shih, Han-Wei
Alas, Germain C.M.
Paredez, Alexander R.
author_facet Shih, Han-Wei
Alas, Germain C.M.
Paredez, Alexander R.
author_sort Shih, Han-Wei
collection PubMed
description Protozoan parasites use cAMP signaling to precisely regulate the place and time of developmental differentiation, yet it is unclear how this signaling is initiated. Encystation of the intestinal parasite Giardia lamblia can be activated by multiple stimuli, which we hypothesize result in a common physiological change. We demonstrate that bile alters plasma membrane fluidity by reducing cholesterol-rich lipid microdomains, while alkaline pH enhances bile function. Through depletion of the cAMP producing enzyme Adenylate Cyclase 2 (AC2) and the use of a newly developed Giardia-specific cAMP sensor, we show that AC2 is necessary for encystation stimuli-induced cAMP upregulation and activation of downstream signaling. Conversely, over expression of AC2 or exogenous cAMP were sufficient to initiate encystation. Our findings indicate that encystation stimuli induce membrane reorganization, trigger AC2-dependent cAMP upregulation, and initiate encystation-specific gene expression, thereby advancing our understanding of a critical stage in the life cycle of a globally important parasite.
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spelling pubmed-101684622023-05-10 Encystation stimuli sensing mediated by adenylate cyclase AC2-dependent cAMP signaling in Giardia Shih, Han-Wei Alas, Germain C.M. Paredez, Alexander R. Res Sq Article Protozoan parasites use cAMP signaling to precisely regulate the place and time of developmental differentiation, yet it is unclear how this signaling is initiated. Encystation of the intestinal parasite Giardia lamblia can be activated by multiple stimuli, which we hypothesize result in a common physiological change. We demonstrate that bile alters plasma membrane fluidity by reducing cholesterol-rich lipid microdomains, while alkaline pH enhances bile function. Through depletion of the cAMP producing enzyme Adenylate Cyclase 2 (AC2) and the use of a newly developed Giardia-specific cAMP sensor, we show that AC2 is necessary for encystation stimuli-induced cAMP upregulation and activation of downstream signaling. Conversely, over expression of AC2 or exogenous cAMP were sufficient to initiate encystation. Our findings indicate that encystation stimuli induce membrane reorganization, trigger AC2-dependent cAMP upregulation, and initiate encystation-specific gene expression, thereby advancing our understanding of a critical stage in the life cycle of a globally important parasite. American Journal Experts 2023-04-25 /pmc/articles/PMC10168462/ /pubmed/37162830 http://dx.doi.org/10.21203/rs.3.rs-2818450/v1 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.
spellingShingle Article
Shih, Han-Wei
Alas, Germain C.M.
Paredez, Alexander R.
Encystation stimuli sensing mediated by adenylate cyclase AC2-dependent cAMP signaling in Giardia
title Encystation stimuli sensing mediated by adenylate cyclase AC2-dependent cAMP signaling in Giardia
title_full Encystation stimuli sensing mediated by adenylate cyclase AC2-dependent cAMP signaling in Giardia
title_fullStr Encystation stimuli sensing mediated by adenylate cyclase AC2-dependent cAMP signaling in Giardia
title_full_unstemmed Encystation stimuli sensing mediated by adenylate cyclase AC2-dependent cAMP signaling in Giardia
title_short Encystation stimuli sensing mediated by adenylate cyclase AC2-dependent cAMP signaling in Giardia
title_sort encystation stimuli sensing mediated by adenylate cyclase ac2-dependent camp signaling in giardia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10168462/
https://www.ncbi.nlm.nih.gov/pubmed/37162830
http://dx.doi.org/10.21203/rs.3.rs-2818450/v1
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