title: A novel Rho-like protein TbRHP is involved in spindle formation and mitosis in trypanosomes.
abstract: BACKGROUND
  In animals and fungi Rho subfamily small GTPases are involved in signal transduction, cytoskeletal function and cellular proliferation. These organisms typically possess multiple Rho paralogues and numerous downstream effectors, consistent with the highly complex contributions of Rho proteins to cellular physiology. By contrast, trypanosomatids have a much simpler Rho-signaling system, and the Trypanosoma brucei genome contains only a single divergent Rho-related gene, TbRHP (Tb927.10.6240). Further, only a single RhoGAP-like protein (Tb09.160.4180) is annotated, contrasting with the >70 Rho GAP proteins from Homo sapiens. We wished to establish the function(s) of TbRHP and if Tb09.160.4180 is a potential GAP for this protein.
  
  
  RESULTS
  TbRHP represents an evolutionarily restricted member of the Rho GTPase clade and is likely trypanosomatid restricted. TbRHP is expressed in both mammalian and insect dwelling stages of T. brucei and presents with a diffuse cytoplasmic location and is excluded from the nucleus. RNAi ablation of TbRHP results in major cell cycle defects and accumulation of multi-nucleated cells, coinciding with a loss of detectable mitotic spindles. Using yeast two hybrid analysis we find that TbRHP interacts with both Tb11.01.3180 (TbRACK), a homolog of Rho-kinase, and the sole trypanosome RhoGAP protein Tb09.160.4180, which is related to human OCRL.
  
  
  CONCLUSIONS
  Despite minimization of the Rho pathway, TbRHP retains an important role in spindle formation, and hence mitosis, in trypanosomes. TbRHP is a partner for TbRACK and an OCRL-related trypanosome Rho-GAP.
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Kanwal
authors.initials: K
authors.lastname: Abbasi
authors.forename: Kelly N
authors.initials: KN
authors.lastname: DuBois
authors.forename: Ka Fai
authors.initials: KF
authors.lastname: Leung
authors.forename: Joel B
authors.initials: JB
authors.lastname: Dacks
authors.forename: Mark C
authors.initials: MC
authors.lastname: Field
mesh_terms: D008938:Mitosis / Q000235:genetics / Q000502:physiology*; D011485:Protein Binding; D015800:Protozoan Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D008941:Spindle Apparatus / Q000378:metabolism*; D014346:Trypanosoma brucei brucei / Q000166:cytology* / Q000235:genetics / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D015800:Protozoan Proteins; D020741:rho GTP-Binding Proteins
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