A genetic model for in vivo proximity labelling of the mammalian secretome

Copyright and License

© 2022 The Authors. Published by the Royal Society under the terms of the Creative Commons AttributionLicense http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the originalauthor and source are credited.

Acknowledgement

We thank the Janelia Gene Targeting and Transgenics Facility (Director: Caiying Guo) for the BirA*G3 mouse generation. We thank Peter Calabrese and Ivy Xiong from University of Southern California (USC), Pierre Michel Jean Beltran from Broad Institute, Xianwen Ren from Peking University, Kevin Blighe from Rancho BioSciences, and Geetu Tuteja from Iowa State University for help with mass spectrometry data analysis. We thank Jeffrey Boyd and Bernadette Masinsin from the Flow Cytometry Facility of Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at USC for assisting with hepatocyte sorting. We thank Seth Ruffins from Optical Imaging Facility and Riana Parvez of Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at USC for assisting with fluorescence imaging. We thank Genome Technology Access Center from Washington University for performing bulk RNA-seq.

Funding

This work was supported by a NIH Transformative R01 grant 5R01DK121409 to A.P.M., A.Y.T., S.A.C. and N.P., and HHMI funding to N.P. I.A.D. acknowledges support from the Ellen Browning Scripps Foundation.

Contributions

R.Y.: conceptualization, data curation, investigation, software, validation, visualization, writing—original draft; A.S.M.: conceptualization, data curation, investigation, software, validation, visualization, writing—original draft; I.A.D.: conceptualization, data curation, software, writing—original draft, writing—review and editing; N.D.U.: conceptualization, data curation, formal analysis, methodology, software; Y.H.: methodology, software, visualization; J.G.: data curation, validation, visualization; J.A.M.: conceptualization, data curation, project administration, visualization; D.K.C.: data curation, methodology, software, visualization; C.X.: data curation, software, visualization; Q.F.: software, visualization; J.S.: data curation, methodology, software; S.Q.: software, visualization; D.R.: data curation, visualization; J.W.: data curation, methodology, writing—review and editing; A.Y.T.: conceptualization, methodology, writing—review and editing; S.A.C.: methodology, software, writing—review and editing; N.P.: conceptualization, project administration, writing—review and editing; A.P.M.: conceptualization, methodology, project administration, writing—original draft, writing—review and editing.

All authors gave final approval for publication and agreed to be held accountable for the work performed therein.

Data Availability

The original mass spectra and the protein sequence databases used for searches have been deposited in the public proteomics repository MassIVE (http://massive.ucsd.edu) and are accessible at ftp://MSV000088848@massive.ucsd.edu. RNA sequencing data is available under BioProject PRJNA808087 from NCBI SRA at https://www.ncbi.nlm.nih.gov/sra. The following public databases were used: Uniprot (https://www.uniprot.org), mouse (https://www.uniprot.org/proteomes/UP000000589), SignalP 5.0 (https://services.healthtech.dtu.dk/service.php?SignalP-5.0), TMHMM 2.0 (https://services.healthtech.dtu.dk/service.php?TMHMM-2.0). All analysis code is available at https://github.com/asmeyer/A-genetic-model-for-in-vivo-proximity-labeling-of-the-mammalian-secretome.git. Corresponding authors will provide original data upon request. Source data are provided with this paper.

The data are provided in electronic supplementary material [62].

Conflict of Interest

A.P.M. is a scientific adviser for Novartis, TRESTLE BioTherapeutics, eGENESIS and IVIVA Medical. S.A.C. is a member of the scientific advisory boards of Kymera, PTM BioLabs, Seer and PrognomIQ. A.Y.T. declares intellectual property interests around proximity labelling technology.

Ethics

Institutional Animal Care and Use Committees (IACUC) at the University of Southern California reviewed and approved all animal work as performed in this study. All work adhered to institutional guidelines.

Supplemental Material

Supplementary material and data sets available on figshare: https://doi.org/10.6084/m9.figshare.c.6125239.v1