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TORC1 is an essential regulator of nutrient-dependent differentiation in Leishmania
TORC1 is an essential regulator of nutrient-dependent differentiation in Leishmania
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Length:
20 minutes
Released:
Oct 21, 2022
Format:
Podcast episode
Description
Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2022.10.20.513059v1?rss=1
Authors: Myburgh, E., Geoghegan, V., Alves-Ferreira, E. V. C., Nievas, Y. R., Grewal, J. S., Brown, E., McLuskey, K., Mottram, J. C.
Abstract:
Leishmania parasites undergo differentiation between various proliferating and non-dividing forms to adapt to changing host environments. The mechanisms that link environmental cues with the parasite's developmental changes remain elusive. Here, we report that Leishmania TORC1 is a key environmental sensor for parasite differentiation in the sand fly-stage promastigotes and for replication of mammalian-stage amastigotes. We show that Leishmania RPTOR1, interacts with TOR1 and LST8. We investigate TORC1 function by conditional deletion of RPTOR1, where under nutrient rich conditions RPTOR1 depletion results in decreased protein synthesis and growth, G1 cell cycle arrest and premature differentiation from proliferative promastigotes to non-dividing mammalian-infective metacyclic forms. These parasites cannot develop into proliferative amastigotes in the mammalian host, or respond to nutrients to differentiate to proliferative retroleptomonads, which are required for their blood-meal induced amplification in sand flies and enhanced mammalian infectivity. RPTOR1-dependent TORC1 functionality represents a critical mechanism for driving parasite growth and proliferation.
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http://biorxiv.org/cgi/content/short/2022.10.20.513059v1?rss=1
Authors: Myburgh, E., Geoghegan, V., Alves-Ferreira, E. V. C., Nievas, Y. R., Grewal, J. S., Brown, E., McLuskey, K., Mottram, J. C.
Abstract:
Leishmania parasites undergo differentiation between various proliferating and non-dividing forms to adapt to changing host environments. The mechanisms that link environmental cues with the parasite's developmental changes remain elusive. Here, we report that Leishmania TORC1 is a key environmental sensor for parasite differentiation in the sand fly-stage promastigotes and for replication of mammalian-stage amastigotes. We show that Leishmania RPTOR1, interacts with TOR1 and LST8. We investigate TORC1 function by conditional deletion of RPTOR1, where under nutrient rich conditions RPTOR1 depletion results in decreased protein synthesis and growth, G1 cell cycle arrest and premature differentiation from proliferative promastigotes to non-dividing mammalian-infective metacyclic forms. These parasites cannot develop into proliferative amastigotes in the mammalian host, or respond to nutrients to differentiate to proliferative retroleptomonads, which are required for their blood-meal induced amplification in sand flies and enhanced mammalian infectivity. RPTOR1-dependent TORC1 functionality represents a critical mechanism for driving parasite growth and proliferation.
Copy rights belong to original authors. Visit the link for more info
Podcast created by Paper Player, LLC
Released:
Oct 21, 2022
Format:
Podcast episode
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