Sorting of secretory proteins at the trans-Golgi network by human TGN46

Author:

Lujan Pablo1,Garcia-Cabau Carla2ORCID,Wakana Yuichi3ORCID,Vera Lillo Javier1,Rodilla-Ramírez Carmen1ORCID,Sugiura Hideaki3,Malhotra Vivek456ORCID,Salvatella Xavier26ORCID,Garcia-Parajo Maria F16ORCID,Campelo Felix1ORCID

Affiliation:

1. ICFO-Institut de Ciencies Fotoniques, The Barcelona Institute of Science and Technology

2. Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology

3. School of Life Sciences, Tokyo University of Pharmacy and Life Sciences

4. Centre for Genomic Regulation, The Barcelona Institute of Science and Technology

5. Universitat Pompeu Fabra

6. Institució Catalana de Recerca i Estudis Avançats (ICREA)

Abstract

Secretory proteins are sorted at the trans-Golgi network (TGN) for export into specific transport carriers. However, the molecular players involved in this fundamental process remain largely elusive. Here, we identified the human transmembrane protein TGN46 as a receptor for the export of secretory cargo protein PAUF in CARTS – a class of protein kinase D-dependent TGN-to-plasma membrane carriers. We show that TGN46 is necessary for cargo sorting and loading into nascent carriers at the TGN. By combining quantitative fluorescence microscopy and mutagenesis approaches, we further discovered that the lumenal domain of TGN46 encodes for its cargo sorting function. In summary, our results define a cellular function of TGN46 in sorting secretory proteins for export from the TGN.

Funder

Ministerio de Ciencia e Innovación

Agencia Estatal de Investigación

European Research Council

Laserlab-Europe

Publisher

eLife Sciences Publications, Ltd

Reference95 articles.

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