Why do Leishmania need a flagellum, and how does it work?

Cilia and flagella are cellular projections built around a microtubule axoneme whose molecular architecture is highly conserved across eukaryotic groups. Cilia and flagella serve two main functions: motility and sensory. Many cell types (ranging from single-celled organisms such as Leishmania to mammalian sperm cells) use their motile flagellum for locomotion. Sensory cilia serve a wide range of functions. In the human body, for example, cilia are important for the detection of developmental signals, and the perception of chemical and mechanical stimuli. Single-celled organisms also use cilia and flagella for detection of signals from the environment.

When the Leishmania parasite is engulfed by a macrophage, it changes shape and we discovered that its flagellum is remodelled from a device built for swimming (with a 9+2 arrangement of axoneme microtubules), into a structure resembling a sensory cilium (with a 9+0 axoneme) (Gluenz et al., 2010; Wheeler et al., 2015). We showed that motility of promastigotes is important for the colonisation of sand flies (Beneke et al., 2019).

We have generated a Leishmania gene deletion library for >500 flagellar proteins, which we are using to study the functions of individual proteins in flagellar motility and to discover the function of cyclic nucleotide signalling in motility regulation.

Funding:

SNSF

MRC / DIFID

Royal Society