CYTOSKELETON AND MOTORS
Cytoskeleton and motors (Morriswood lab)
The hook complex
The hook complex is an enigmatic cytoskeleton-associated structure that appears to regulate macromolecule entry into the cell.
Trypanosome actomyosin system
Trypanosomes have a highly reduced actomyosin system relative to metazoa. The functions of its myosin motors are still largely unclear.
The trypanosome hook complex may control entry into the trypanosome's flagellar pocket
A trypanosome cell has a single external flagellum whose base is anchored in an invagination of the plasma membrane called the flagellar pocket. The flagellar pocket is the site of all endocytosis and exocytosis in the cell, making it the nexus of the parasite’s interaction with its host in both a nutritional and an immunological context.
Clustered around the neck of the flagellar pocket are a number of cytoskeletal complexes whose functionality is almost completely unexplored. Of principal interest to the Morriswood group is the hook complex, a fishhook-shaped multiprotein assembly containing the repeat motif protein TbMORN1. Previous work has deciphered the morphology of the complex using a combination of fluorescence microscopy and electron microscopy, and its composition has been partly determined using proximity-dependent biotin identification (BioID).
Recent functional work has implicated the hook complex in the entry of material into the flagellar pocket, suggesting that it might function as a kind of molecular valve. Current work in the group is focused on testing and refining this hypothesis, and extending the observations to other components of the hook complex.
Trypanosomes have heavily invested in their microtubule-based cytoskeleton
... with a microtubule corset underlying the plasma membrane, a flagellar axoneme, and several other microtubule-based structures (mitotic spindle, microtubule quartet, basal body). They correspondingly express a huge (>40) number of kinesin motor proteins – more even than human cells.
Conversely, the actin-based cytoskeleton is extremely reduced, with many actin regulators completely absent and only two myosin motor proteins encoded in Trypanosoma brucei and Leishmania species.
In effect, trypanosomes can be regarded as organisms that have done everything possible to eliminate actomyosin-based cytoskeletal functionality – and yet they have still retained a minimal set of actin and myosin motor protein genes.
This suggests that the actomyosin system can perform one or more functions which the microtubule-based cytoskeleton cannot recapitulate. Determining what those function(s) are will be of profound interest to eukaryotic cytoskeleton biology. In addition, such an extremely reduced system makes trypanosomes an ideal model system (in effect, a living laboratory) to address fundamental questions about myosin motor protein function in eukaryotes.