A Putative cAMP-Binding Protein in Trypanosoma brucei Cooperates With FLAM3 to Promote Flagellar Connection and Cell Morphogenesis

Authors

Qing Zhou
Phu Van Nguyen
Ziyin Li

Publication Date

11-1-2024

Journal

Journal of Biological Chemistry

Abstract

Trypanosoma brucei is a flagellated parasitic protozoan, and within the insect vector the parasite transitions from the trypomastigote form to the epimastigote form by repositioning its mitochondrial genome and relocating the flagellum. The mechanisms underlying such morphology changes are still poorly understood, but several flagellum-localized proteins are involved in this process by modulating the flagellum attachment zone (FAZ) that adheres the flagellum to the cell membrane. We report here a putative cAMP-binding protein named cAMP-BP1, which promotes flagellar connection and morphology transition. cAMP-BP1 contains two cyclic nucleotide-binding domains and five calcium-binding C2 domains and localizes to the flagella connector and the new FAZ tip. Depletion of cAMP-BP1 in the trypomastigote form of T. brucei causes major morphology changes, generating epimastigote-like cells with repositioned kinetoplast and relocated flagellum. At the flagella connector and the new FAZ tip, cAMP-BP1 associates with FLAM3, a regulator of morphology transition, depends on the latter for localization, and is required for FLAM3 localization to the flagella connector. Knockdown of cAMP-BP1 inhibits FAZ elongation and disrupts flagellar connection by impairing flagella connector structural integrity. These results identify a flagella connector- and new FAZ tip-localized protein as a regulator of morphology transition and flagellar connection in trypanosomes and uncover its functional interplay with FLAM3 to promote FAZ elongation for maintaining trypomastigote morphology.

Keywords

Trypanosoma brucei brucei, Flagella, Protozoan Proteins, Morphogenesis, Cyclic AMP

Comments

This article has been corrected. See J Biol Chem. 2025 Feb 16;301(3):108238.

DOI

10.1016/j.jbc.2024.107856

PMID

39369991

PMCID

PMC11555346

PubMedCentral® Posted Date

10-5-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes