TY - JOUR
T1 - A multi-adenylate cyclase regulator at the flagellar tip controls African trypanosome transmission
AU - Bachmaier, Sabine
AU - Giacomelli, Giacomo
AU - Calvo-Alvarez, Estefania
AU - Vieira, Larissa Rezende
AU - Van Den Abbeele, Jan
AU - Aristodemou, Aris
AU - Lorentzen, Esben
AU - Gould, Matthew
AU - Brennand, Ana
AU - Dupuy, Jean-Wiliam
AU - Forne, Ignasi
AU - Imhof, Axel
AU - Bramkamp, Marc
AU - Salmon, Didier
AU - Rotureau, Brice
AU - Boshart, Michael
N1 - FTX; DOAJ; (CC BY 4.0)
PY - 2022
Y1 - 2022
N2 - Signaling from ciliary microdomains controls developmental processes in metazoans. Trypanosome transmission requires development and migration in the tsetse vector alimentary tract. Flagellar cAMP signaling has been linked to parasite social motility (SoMo) in vitro, yet uncovering control of directed migration in fly organs is challenging. Here we show that the composition of an adenylate cyclase (AC) complex in the flagellar tip microdomain is essential for tsetse salivary gland (SG) colonization and SoMo. Cyclic AMP response protein 3 (CARP3) binds and regulates multiple AC isoforms. CARP3 tip localization depends on the cytoskeletal protein FLAM8. Re-localization of CARP3 away from the tip microdomain is sufficient to abolish SoMo and fly SG colonization. Since intrinsic development is normal in carp3 and flam8 knock-out parasites, AC complex-mediated tip signaling specifically controls parasite migration and thereby transmission. Participation of several developmentally regulated receptor-type AC isoforms may indicate the complexity of the in vivo signals perceived.
AB - Signaling from ciliary microdomains controls developmental processes in metazoans. Trypanosome transmission requires development and migration in the tsetse vector alimentary tract. Flagellar cAMP signaling has been linked to parasite social motility (SoMo) in vitro, yet uncovering control of directed migration in fly organs is challenging. Here we show that the composition of an adenylate cyclase (AC) complex in the flagellar tip microdomain is essential for tsetse salivary gland (SG) colonization and SoMo. Cyclic AMP response protein 3 (CARP3) binds and regulates multiple AC isoforms. CARP3 tip localization depends on the cytoskeletal protein FLAM8. Re-localization of CARP3 away from the tip microdomain is sufficient to abolish SoMo and fly SG colonization. Since intrinsic development is normal in carp3 and flam8 knock-out parasites, AC complex-mediated tip signaling specifically controls parasite migration and thereby transmission. Participation of several developmentally regulated receptor-type AC isoforms may indicate the complexity of the in vivo signals perceived.
KW - Adenylyl Cyclases/metabolism
KW - Animals
KW - Cyclic AMP
KW - Trypanosoma
KW - Trypanosoma brucei brucei/metabolism
KW - Tsetse Flies/parasitology
U2 - 10.1038/s41467-022-33108-z
DO - 10.1038/s41467-022-33108-z
M3 - A1: Web of Science-article
C2 - 36114198
SN - 2041-1723
VL - 13
SP - 5445
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 5445
ER -