The flagellar pocket neck of Trypanosoma brucei: a multifunctional plasma membrane subdomain.

• Applicant: Privatdozent Dr. Brooke Morriswood
• Subject Area: Cell Biology ; Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2018 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 396187369

The plasma membrane of eukaryotic cells is composed of various subdomains. The protist Trypanosoma brucei, a single-celled parasite that is responsible for sleeping sickness, exhibits a potentially unique paradigm for plasma membrane subdomain organisation. The single flagellum of T. brucei is anchored at its root in a deep invagination of the plasma membrane called the flagellar pocket. The flagellar pocket is the sole site of endo- and exocytosis, and thus represents the hub of the parasite's interaction with its mammalian hosts. It is essential that nutrients and host antibodies that have bound to the surface glycoprotein coat can efficiently enter the flagellar pocket to be internalised. Conversely, a number of scavenger proteins have a privileged localisation within the flagellar pocket and need to be retained there.At the centre of this delicate balance is the flagellar pocket neck, a cylindrical subdomain of the plasma membrane that links the flagellar pocket with the surface plasma membrane. The flagellar pocket neck is tightly apposed (in trans) with the membrane encasing the flagellum, and contiguous (i.e. in cis-apposition) with the flagellar pocket. Underlying the cytoplasmic face of the flagellar pocket neck is the hook complex, a cytoskeleton-associated protein assembly that appears to regulate the function of the flagellar pocket neck.This proposal seeks to understand the operation of the flagellar pocket neck subdomain, its cis and trans interactions with the flagellar pocket and flagellar membrane, and the regulation of these processes by the hook complex. The proposed experiments will examine the exclusion limits of inbound traffic, the retention mechanisms within the flagellar pocket, and the protein composition of the hook complex and its means of cytoskeleton association.

• DFG Programme: Research Grants