Signaling from ciliary nanodomains 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 architecture of an adenylate cyclase (AC) complex in the flagellar tip nanodomain 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 scaffold FLAM8. Re-localization of CARP3 away from the tip nanodomain is sufficient to abolish SoMo and fly SG colonization. Since intrinsic development is normal in ∆carp3 and ∆flam8 mutant 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.