Reese Lab Publications

Cryo-FIB/cryo-ET of the coccidian invasion machinery

Gui L, O'Shaughnessy WJ, Cai K, Reetz E, Reese ML, Nicastro D. Cryo-tomography reveals rigid-body motion and organization of apicomplexan invasion machinery. (2023) Nat Commun. 14(1):1775. PMID: 36997532. PMCID: PMC10063558 (also as: bioRxiv preprint)
In this collaboration with the Nicastro Lab (also at UTSW), we used cryo-focused-ion-beam (cryo-FIB) milling and cryo-electron tomography (cryo-ET) to get structural information of the parasite invasion machinery in its native state – from intact cells! This combination of techniques allows us to get unprecedented information about the organization of the secretory and cytoskeletal components most crucial to the Apicomplexan parasitic lifestyle. One ongoing project in the lab is working to gain a higher resolution understanding of these protein complexes by combining modelling, crystallography, single-particle cryo-EM, and cryo-ET. If that sounds cool, contact us about joining!

Identification of an E3 ligase required for cytoskeletal turnover during Toxoplasma division.

O'Shaughnessy WJ, Hu X, Henriquez SA, Reese ML. Toxoplasma ERK7 protects the apical complex from premature degradation. (2023) J Cell Biol. 222(6) PMID: 37027006. PMCID: PMC10083718 (also as: bioRxiv preprint)
We had previously found that loss of ERK7 function caused destruction of the organizing core of the Toxoplasma invasion machinery, a structure called the conoid. We started this project looking for the protein downstream of ERK7 that was responsible for this phenotype, assuming that ERK7 activated something that promoted conoid assembly & maturation. To our surprise, we identified a protein that is required for degradation of the conoid and other maternal cytoskeleton during parasite division. That is, it appears ERK7 inhibits this protein, a putative E3 ubiquitin ligase which we named CSAR1. Without functional ERK7, CSAR1 goes haywire, and degrades more things than it should. This discovery also highlighted a potentially critical role of the parasite residual body in regulating protein homeostasis, which had not previously been considered.

A Toxoplasma MAP kinase required for maturation of the invasion machinery

O'Shaughnessy WJ, Hu X, Beraki T, McDougal M, Reese ML. Loss of a conserved MAPK causes catastrophic failure in assembly of a specialized cilium-like structure in Toxoplasma gondii. (2020) Mol Biol Cell. 31(9):881-888. PMID: 32073987. PMCID: PMC7185968 (also as: bioRxiv preprint).
This paper identified the MAPK, ERK7, as required for the maturation of the conoid, a specialized tubulin structure that appears to have evolved from a eukaryotic cilium. The conoid is absolutely essential for Toxoplasma to infect cells, so its loss results parasites that are trapped outside of host cells. This was the first discovery of a non-structural protein that disrupted the structure of the conoid.

Function of a divergent secreted kinase in parasitophorous vacuole biogenesis

Beraki T, Hu X, Broncel M, Young JC, O'Shaughnessy WJ, Borek D, Treeck M, Reese ML. Divergent kinase regulates membrane ultrastructure of the Toxoplasma parasitophorous vacuole. (2019) Proc Natl Acad Sci U S A. 116(13):6361-6370. PMID: 30850550. PMCID: PMC6442604 (also as: bioRxiv preprint).  
In this paper, we identified an unusual kinase family that lacks a Gly-loop or "Walker motif" which is normally essential to kinase function. In spite of this, these kinases are catalytically active. We went on to demonstrate that the most well-conserved member of this family (the "With-no-Gly-loop" or "WNG" family), a protein called WNG1, was essential for the phosphorylation of a number of proteins secreted into the Toxoplasma parasitophorous vacuole. Furthermore, without this kinase, these proteins were unable to insert into the vacuole membrane, which disrupted the biogenesis of this specialized organelle.
  1. Kumar A, Gok MO, Nguyen KN, Connor OM, Reese ML, Wideman JG, Munoz-Gomez SA, Friedman JR. A dynamin superfamily-like pseudoenzyme coordinates with MICOS to promote cristae architecture. (2024) Curr Biol. PMID: 38692277 (also as: bioRxiv preprint)
  2. O'Shaughnessy WJ, Hu X, Henriquez SA, Reese ML. Toxoplasma ERK7 protects the apical complex from premature degradation. (2023) J Cell Biol. 222(6) PMID: 37027006. PMCID: PMC10083718 (also as: bioRxiv preprint)
  3. Gui L, O'Shaughnessy WJ, Cai K, Reetz E, Reese ML, Nicastro D. Cryo-tomography reveals rigid-body motion and organization of apicomplexan invasion machinery. (2023) Nat Commun. 14(1):1775. PMID: 36997532. PMCID: PMC10063558 (also as: bioRxiv preprint)  
  4. O'Shaughnessy WJ, Dewangan PS, Paiz EA, Reese ML. Not your Mother's MAPKs: Apicomplexan MAPK function in daughter cell budding. (2022) PLoS Pathog. 18(10):e1010849. PMID: 36227859. PMCID: PMC9560070
  5. Dewangan PS, Beraki TG, Paiz EA, Appiah Mensah D, Chen Z, Reese ML. Divergent kinase WNG1 is regulated by phosphorylation of an atypical activation sub-domain. (2022) Biochem J. 479(17):1877-1889. PMID: 35938919. PMCID: PMC9555795 (also as: bioRxiv preprint)
  6. Wendt GR, Reese ML, Collins JJ 3rd. SchistoCyte Atlas: A Single-Cell Transcriptome Resource for Adult Schistosomes. (2021) Trends Parasitol. 37(7):585-587. PMID: 33975779. PMCID: PMC8721880
  7. Xia J, Venkat A, Bainbridge RE, Reese ML, Le Roch KG, Ay F, Boyle JP. Third-generation sequencing revises the molecular karyotype for Toxoplasma gondii and identifies emerging copy number variants in sexual recombinants. (2021) Genome Res. 31(5):834-851. PMID: 33906962. PMCID: PMC8092015 (also as: bioRxiv preprint)
  8. Back PS, O'Shaughnessy WJ, Moon AS, Dewangan PS, Reese ML, Bradley PJ. Multivalent Interactions Drive the Toxoplasma AC9:AC10:ERK7 Complex To Concentrate ERK7 in the Apical Cap. (2021) mBio. 13(1):e0286421. PMID: 35130732. PMCID: PMC8822341 (also as: bioRxiv preprint)
  1. Hu X, O'Shaughnessy WJ, Beraki TG, Reese ML. Loss of the Conserved Alveolate Kinase MAPK2 Decouples Toxoplasma Cell Growth from Cell Division. (2020) mBio. 11(6) PMID: 33173004. PMCID: PMC7667025 (also as: bioRxiv preprint)
  2. Wendt G, Zhao L, Chen R, Liu C, O'Donoghue AJ, Caffrey CR, Reese ML, Collins JJ 3rd. A single-cell RNA-seq atlas of Schistosoma mansoni identifies a key regulator of blood feeding. (2020) Science. 369(6511):1644-1649. PMID: 32973030. PMCID: PMC7875187
  3. Kongsomboonvech AK, Rodriguez F, Diep AL, Justice BM, Castallanos BE, Camejo A, Mukhopadhyay D, Taylor GA, Yamamoto M, Saeij JPJ, Reese ML, Jensen KDC. Naive CD8 T cell IFNgamma responses to a vacuolar antigen are regulated by an inflammasome-independent NLRP3 pathway and Toxoplasma gondii ROP5. (2020) PLoS Pathog. 16(8):e1008327. PMID: 32853276. PMCID: PMC7480859 (also as: bioRxiv preprint)
  4. Back PS, O'Shaughnessy WJ, Moon AS, Dewangan PS, Hu X, Sha J, Wohlschlegel JA, Bradley PJ, Reese ML. Ancient MAPK ERK7 is regulated by an unusual inhibitory scaffold required for Toxoplasma apical complex biogenesis. (2020) Proc Natl Acad Sci U S A. 117(22):12164-12173. PMID: 32409604. PMCID: PMC7275706 (also as: bioRxiv preprint)  
  5. O'Shaughnessy WJ, Hu X, Beraki T, McDougal M, Reese ML. Loss of a conserved MAPK causes catastrophic failure in assembly of a specialized cilium-like structure in Toxoplasma gondii. (2020) Mol Biol Cell. 31(9):881-888. PMID: 32073987. PMCID: PMC7185968 (also as: bioRxiv preprint)
  6. Park BC, Reese M, Tagliabracci VS. Thinking outside of the cell: Secreted protein kinases in bacteria, parasites, and mammals. (2019) IUBMB Life. 71(6):749-759. PMID: 30941842. PMCID: PMC7967855
  7. Beraki T, Hu X, Broncel M, Young JC, O'Shaughnessy WJ, Borek D, Treeck M, Reese ML. Divergent kinase regulates membrane ultrastructure of the Toxoplasma parasitophorous vacuole. (2019) Proc Natl Acad Sci U S A. 116(13):6361-6370. PMID: 30850550. PMCID: PMC6442604 (also as: bioRxiv preprint)  
  8. Henne WM, Reese ML, Goodman JM. The assembly of lipid droplets and their roles in challenged cells. (2018) EMBO J. 37(12) PMID: 29789390. PMCID: PMC6003646
  9. Hu X, Binns D, Reese ML. The coccidian parasites Toxoplasma and Neospora dysregulate mammalian lipid droplet biogenesis. (2017) J Biol Chem. 292(26):11009-11020. PMID: 28487365. PMCID: PMC5491784
  10. Child MA, Garland M, Foe I, Madzelan P, Treeck M, van der Linden WA, Oresic Bender K, Weerapana E, Wilson MA, Boothroyd JC, Reese ML, Bogyo M. Toxoplasma DJ-1 Regulates Organelle Secretion by a Direct Interaction with Calcium-Dependent Protein Kinase 1. (2017) mBio. 8(1) PMID: 28246362. PMCID: PMC5347346
  11. Reese ML, Shah N, Boothroyd JC. The Toxoplasma pseudokinase ROP5 is an allosteric inhibitor of the immunity-related GTPases. (2014) J Biol Chem. 289(40):27849-58. PMID: 25118287. PMCID: PMC4183819
  12. Grover HS, Chu HH, Kelly FD, Yang SJ, Reese ML, Blanchard N, Gonzalez F, Chan SW, Boothroyd JC, Shastri N, Robey EA. Impact of regulated secretion on antiparasitic CD8 T cell responses. (2014) Cell Rep. 7(5):1716-1728. PMID: 24857659. PMCID: PMC4057976
  13. Gaji RY, Checkley L, Reese ML, Ferdig MT, Arrizabalaga G. Expression of the essential Kinase PfCDPK1 from Plasmodium falciparum in Toxoplasma gondii facilitates the discovery of novel antimalarial drugs. (2014) Antimicrob Agents Chemother. 58(5):2598-607. PMID: 24550330. PMCID: PMC3993251
  14. Murphy JM, Zhang Q, Young SN, Reese ML, Bailey FP, Eyers PA, Ungureanu D, Hammaren H, Silvennoinen O, Varghese LN, Chen K, Tripaydonis A, Jura N, Fukuda K, Qin J, Nimchuk Z, Mudgett MB, Elowe S, Gee CL, Liu L, Daly RJ, Manning G, Babon JJ, Lucet IS. A robust methodology to subclassify pseudokinases based on their nucleotide-binding properties. (2014) Biochem J. 457(2):323-34. PMID: 24107129. PMCID: PMC5679212
  15. Reese ML. Immune to defeat. (2013) Elife. 2:e01599. PMID: 24175089. PMCID: PMC3810862
  1. Reese ML, Boyle JP. Virulence without catalysis: how can a pseudokinase affect host cell signaling? (2012) Trends Parasitol. 28(2):53-7. PMID: 22257555
  2. Fleckenstein MC, Reese ML, Konen-Waisman S, Boothroyd JC, Howard JC, Steinfeldt T. A Toxoplasma gondii pseudokinase inhibits host IRG resistance proteins. (2012) PLoS Biol. 10(7):e1001358. PMID: 22802726. PMCID: PMC3393671
  3. Reese ML, Boothroyd JC. A conserved non-canonical motif in the pseudoactive site of the ROP5 pseudokinase domain mediates its effect on Toxoplasma virulence. (2011) J Biol Chem. 286(33):29366-29375. PMID: 21708941. PMCID: PMC3190742
  4. Hall CI, Reese ML, Weerapana E, Child MA, Bowyer PW, Albrow VE, Haraldsen JD, Phillips MR, Sandoval ED, Ward GE, Cravatt BF, Boothroyd JC, Bogyo M. Chemical genetic screen identifies Toxoplasma DJ-1 as a regulator of parasite secretion, attachment, and invasion. (2011) Proc Natl Acad Sci U S A. 108(26):10568-73. PMID: 21670272. PMCID: PMC3127939
  5. Reese ML, Zeiner GM, Saeij JP, Boothroyd JC, Boyle JP. Polymorphic family of injected pseudokinases is paramount in Toxoplasma virulence. (2011) Proc Natl Acad Sci U S A. 108(23):9625-30. PMID: 21436047. PMCID: PMC3111280
  6. Kodama Y, Reese ML, Shimba N, Ono K, Kanamori E, Dotsch V, Noguchi S, Fukunishi Y, Suzuki E, Shimada I, Takahashi H. Rapid identification of protein-protein interfaces for the construction of a complex model based on multiple unassigned signals by using time-sharing NMR measurements. (2011) J Struct Biol. 174(3):434-42. PMID: 21501688
  7. Ong YC, Reese ML, Boothroyd JC. Toxoplasma rhoptry protein 16 (ROP16) subverts host function by direct tyrosine phosphorylation of STAT6. (2010) J Biol Chem. 285(37):28731-40. PMID: 20624917. PMCID: PMC2937901
  8. Reese ML, Boothroyd JC. A helical membrane-binding domain targets the Toxoplasma ROP2 family to the parasitophorous vacuole. (2009) Traffic. 10(10):1458-70. PMID: 19682324. PMCID: PMC2746882
  1. Reese ML, Dakoji S, Bredt DS, Dotsch V. The guanylate kinase domain of the MAGUK PSD-95 binds dynamically to a conserved motif in MAP1a. (2007) Nat Struct Mol Biol. 14(2):155-63. PMID: 17220895
  2. Reese ML, Dotsch V. Fast mapping of protein-protein interfaces by NMR spectroscopy. (2003) J Am Chem Soc. 125(47):14250-1. PMID: 14624553
  3. Chen CY, Reese ML, Hwang PK, Ota N, Agard D, Brodsky FM. Clathrin light and heavy chain interface: alpha-helix binding superhelix loops via critical tryptophans. (2002) EMBO J. 21(22):6072-82. PMID: 12426379. PMCID: PMC137186