Black, J. A., Klinger, C. M., Lemgruber, L. , Dacks, J. B., Mottram, J. C. and McCulloch, R. (2023) AAK1-like: a putative pseudokinase with potential roles in cargo uptake in bloodstream form Trypanosoma brucei parasites. Journal of Eukaryotic Microbiology, 70(6), e12994. (doi: 10.1111/jeu.12994) (PMID:37548427)
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Abstract
Selection and internalization of cargo via clathrin-mediated endocytosis requires adaptor protein complexes. One complex, AP-2, acts during cargo selection at the plasma membrane. African trypanosomes lack all components of the AP-2 complex, except for a recently identified orthologue of the AP-2-associated protein kinase 1, AAK1. In characterized eukaryotes, AAK1 phosphorylates the μ2 subunit of the AP-2 complex to enhance cargo recognition and uptake into clathrin-coated vesicles. Here, we show that kinetoplastids encode not one, but two AAK1 orthologues: one (AAK1L2) is absent from salivarian trypanosomes, while the other (AAK1L1) lacks important kinase-specific residues in a range of trypanosomes. These AAK1L1 and AAK1L2 novelties reinforce suggestions of functional divergence in endocytic uptake within salivarian trypanosomes. Despite this, we show that AAK1L1 null mutant Trypanosoma brucei, while viable, display slowed proliferation, morphological abnormalities including swelling of the flagellar pocket, and altered cargo uptake. In summary, our data suggest an unconventional role for a putative pseudokinase during endocytosis and/or vesicular trafficking in T. brucei, independent of AP-2.
| Item Type: | Articles |
|---|---|
| Additional Information: | This work was supported by the BBSRC [BB/K006495/1, BB/M028909/1, BB/N016165/1, BBW001101/1 and a DTP studentship to JAB], the MRC [MR/S019472/1] and the Wellcome Trust [224501/Z/21/Z to RMcC]. CMK was funded by an Alberta Innovates Health Solutions Fulltime Studentship and a Canada Vanier Graduate Scholarship. The Wellcome Centre for Integrative Parasitology is supported by core funding from the Wellcome Trust [104111}. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Black, Dr Jennifer Ann and Klinger, Christen and McCulloch, Professor Richard and Lemgruber Soares, Dr Leandro |
| Authors: | Black, J. A., Klinger, C. M., Lemgruber, L., Dacks, J. B., Mottram, J. C., and McCulloch, R. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Journal of Eukaryotic Microbiology |
| Publisher: | Wiley |
| ISSN: | 1066-5234 |
| ISSN (Online): | 1550-7408 |
| Published Online: | 07 August 2023 |
| Copyright Holders: | Copyright © 2023 The Authors |
| First Published: | First published in Journal of Eukaryotic Microbiology 2023 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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