@article{Schoellkopf_Mueller_Hippchen-Genom_wide_CRISP-2022,
author = {Schöllkopf, Julian and Mueller, Thomas and Hippchen, Lena 
          and Müller, 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},
doi = {10.1371/journal.ppat.1010781},
volume = {18},
user = {backofen},
pmid = {36516199},
pages = {e1010781},
number = {12},
issn = {1553-7366},
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.}
}