@Article{Schoellkopf_Mueller_Hippchen-Genom_wide_CRISP-2022,
  author =	 {Schoellkopf, Julian and Mueller, Thomas and Hippchen, Lena 
                  and Mueller, Teresa and Reuten, Raphael and Backofen, Rolf 
                  and Orth, Joachim and Schmidt, Gudula},
  title =	 {Genome wide {CRISPR} screen for {Pasteurella} multocida 
                  toxin ({PMT}) binding proteins reveals {LDL} {Receptor} 
                  {Related} {Protein} 1 ({LRP1}) as crucial cellular receptor},
  journal =	 {PLoS Pathog},
  year =	 {2022},
  volume =	 {18},
  number =	 {12},
  pages =	 {e1010781},
  user =	 {backofen},
  pmid =	 {36516199},
  doi = 	 {10.1371/journal.ppat.1010781},
  issn = 	 {1553-7366},
  issn = 	 {1553-7374},
  abstract =	 {PMT is a protein toxin produced by Pasteurella multocida 
                  serotypes A and D. As causative agent of atrophic rhinitis 
                  in swine, it leads to rapid degradation of the nasal 
                  turbinate bone. The toxin acts as a deamidase to modify a 
                  crucial glutamine in heterotrimeric G proteins, which 
                  results in constitutive activation of the G proteins and 
                  permanent stimulation of numerous downstream signaling 
                  pathways. Using a lentiviral based genome wide CRISPR 
                  knockout screen in combination with a lethal toxin chimera, 
                  consisting of full length inactive PMT and the catalytic 
                  domain of diphtheria toxin, we identified the LRP1 gene 
                  encoding the Low-Density Lipoprotein Receptor-related 
                  protein 1 as a critical host factor for PMT function. Loss 
                  of LRP1 reduced PMT binding and abolished the cellular 
                  response and deamidation of heterotrimeric G proteins, 
                  confirming LRP1 to be crucial for PMT uptake. Expression of 
                  LRP1 or cluster 4 of LRP1 restored intoxication of the 
                  knockout cells. In summary our data demonstrate LRP1 as 
                  crucial host entry factor for PMT intoxication by acting as 
                  its primary cell surface receptor.}
}