The proteasome of the differently-diverged eukaryote Giardia lamblia and its role in remodeling of the microtubule-based cytoskeleton

Abstract

Giardia lamblia is the causative agent of the diarrheal disease giardiasis, against which only a limited number of drugs are currently available. Increasing reports of resistance to these drugs makes it necessary to identify new cellular targets for designing the next generation of anti-giardial drugs. Towards this goal, therapeutic agents that target the parasitic cellular machinery involved in the functioning of the unique microtubule-based cytoskeleton of the Giardia trophozoites are likely to be effective as microtubule function is not only important for the survival of trophozoites within the host, but also their extensive remodeling is necessary during the transition from trophozoites to cysts. Thus, drugs that affect microtubule remodeling have the potential to not only kill the disease-causing trophozoites, but also inhibit transmission of cysts in the community. Recent studies in other model organisms have indicated that the proteasome plays an integral role in the formation and remodeling of the microtubule-based cytoskeleton. This review draws attention to the various processes by which the giardial proteasome may impact the functioning of its microtubule cytoskeleton and highlights the possible differences of the parasitic proteasome and some of other cellular machinery involved in microtubule remodeling, compared to that of the higher eukaryotic host.

Keywords:

• Giardia lamblia
• ubiquitin-proteasome system
• intraflagellar transport
• proteasome inhibitor
• cytoskeleton

Acknowledgements

The authors thank Dr. Alok Kumar Sil, Dr. Sudipto Saha and members of the Sarkar Laboratory for their valuable suggestion in improving the quality of the manuscript and Dr. Parna Gupta Bhattacharyya for help with figure preparation.

Disclosure statement

The authors report no declaration of interest.

Additional information

Funding

This work was supported by Department of Biotechnology, Govt. of India [BT/PR3116/BRB/10/957/2011], University Grants Commission [R/198/13] and Bose Institute.