Continuous endosomes form functional subdomains and orchestrate rapid membrane trafficking in trypanosomes

Abstract

Endocytosis is a common process observed in all eukaryotic cells, although its complexity varies among different organisms. In Trypanosoma brucei, the endocytic machinery is under special selective pressure because rapid membrane recycling is essential for immune escape. This unicellular parasite effectively removes host antibodies from its cell surface through hydrodynamic drag and fast endocytic internalization. The entire process of membrane recycling occurs exclusively through the flagellar pocket, an extracellular organelle situated at the posterior pole of the spindle-shaped cell. The high-speed dynamics of membrane flux in trypanosomes do not seem compatible with the conventional concept of distinct compartments for early, late and recycling endosomes. To investigate the underlying structural basis for the remarkably efficient membrane traffic in trypanosomes, we employed advanced techniques in light and electron microscopy to examine the three-dimensional architecture of the endosomal system. Our findings reveal that the endosomal system in trypanosomes exhibits a remarkably intricate structure. Instead of being compartmentalized, it constitutes a continuous membrane system, with specific functions of the endosome segregated into membrane subdomains enriched with classical markers for early, late, and recycling endosomes. These membrane subdomains can partly overlap or are interspersed with areas that are negative for endosomal markers. This continuous endosome allows fast membrane flux by facilitated diffusion that is not slowed by multiple fission and fusion events. Our study further suggests that in trypanosomes, the endosome has taken over the role of the trans-Golgi network as the master regulator of membrane trafficking.

How are Trypanosoma brucei receptors protected from host antibody‐mediated attack?

“…(B) Endocytosis starts via clathrin coated vesicles that are transported to the endosome, a continuous membrane network compartmentalized into distinct functional subdomains with the presence of early, late, or recycling endosomal markers. [ 31 ] The ligand delivered to Rab5 marked early endosome is carried to Rab7 positive late endosome from where a vesicle may bud out to deliver the cargo to lysosome, otherwise, Rab11 marked endosome can recycle the ligand back to the flagellar pocket to rejoin the plasma membrane.…”

“…The compartments associated with handling endocytosed cargo are arrayed between the flagellar pocket and nucleus, with the lysosome normally located distal to the flagellar pocket and proximal to the nucleus. [ 31 ] The endocytosis of VSGs and plasma membrane through the flagellar pocket occurs via class I clathrin coated vesicles (CCV) which migrate to the Rab5 positive early endosome. The next step is either trafficking to Rab11 marked recycling endosomes or to Rab7 positive late compartments [ 29–31 ] (Figure 1B).…”

“…[ 31 ] The endocytosis of VSGs and plasma membrane through the flagellar pocket occurs via class I clathrin coated vesicles (CCV) which migrate to the Rab5 positive early endosome. The next step is either trafficking to Rab11 marked recycling endosomes or to Rab7 positive late compartments [ 29–31 ] (Figure 1B). Estimates for the VSG half‐life, up to 30 h equivalent to five cell doublings, indicate it is recycled many times.…”