Regulation of the COPII secretory machinery via focal adhesions and extracellular matrix signaling

Juan Jung; Muzamil Majid Khan; Jonathan Landry; Aliaksandr Halavatyi; Pedro Machado; Miriam Reiss; Rainer Pepperkok

doi:10.1083/jcb.202110081

Regulation of the COPII secretory machinery via focal adhesions and extracellular matrix signaling

Juan Jung^*, Muzamil Majid Khan, Jonathan Landry, Aliaksandr Halavatyi, Pedro Machado, Miriam Reiss, Rainer Pepperkok

^*Corresponding author for this work

Centre for Ultrastructural Imaging

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

Abstract

Proteins that enter the secretory pathway are transported from their place of synthesis in the endoplasmic reticulum to the Golgi complex by COPII-coated carriers. The networks of proteins that regulate these components in response to extracellular cues have remained largely elusive. Using high-throughput microscopy, we comprehensively screened 378 cytoskeletonassociated and related proteins for their functional interaction with the coat protein complex II (COPII) components SEC23A and SEC23B. Among these, we identified a group of proteins associated with focal adhesions (FERMT2, MACF1, MAPK8IP2, NGEF, PIK3CA, and ROCK1) that led to the downregulation of SEC23A when depleted by siRNA. Changes in focal adhesions induced by plating cells on ECM also led to the downregulation of SEC23A and decreases in VSVG transport from ER to Golgi. Both the expression of SEC23A and the transport defect could be rescued by treatment with a focal adhesion kinase inhibitor. Altogether, our results identify a network of cytoskeleton-associated proteins connecting focal adhesions and ECM-related signaling with the gene expression of the COPII secretory machinery and trafficking.

Original language	English
Article number	e202110081
Journal	Journal of Cell Biology
Volume	221
Issue number	8
DOIs	https://doi.org/10.1083/jcb.202110081
Publication status	Published - 1 Aug 2022

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title = "Regulation of the COPII secretory machinery via focal adhesions and extracellular matrix signaling",

abstract = "Proteins that enter the secretory pathway are transported from their place of synthesis in the endoplasmic reticulum to the Golgi complex by COPII-coated carriers. The networks of proteins that regulate these components in response to extracellular cues have remained largely elusive. Using high-throughput microscopy, we comprehensively screened 378 cytoskeletonassociated and related proteins for their functional interaction with the coat protein complex II (COPII) components SEC23A and SEC23B. Among these, we identified a group of proteins associated with focal adhesions (FERMT2, MACF1, MAPK8IP2, NGEF, PIK3CA, and ROCK1) that led to the downregulation of SEC23A when depleted by siRNA. Changes in focal adhesions induced by plating cells on ECM also led to the downregulation of SEC23A and decreases in VSVG transport from ER to Golgi. Both the expression of SEC23A and the transport defect could be rescued by treatment with a focal adhesion kinase inhibitor. Altogether, our results identify a network of cytoskeleton-associated proteins connecting focal adhesions and ECM-related signaling with the gene expression of the COPII secretory machinery and trafficking.",

author = "Juan Jung and Khan, {Muzamil Majid} and Jonathan Landry and Aliaksandr Halavatyi and Pedro Machado and Miriam Reiss and Rainer Pepperkok",

note = "Funding Information: J. Jung was funded by a fellowship from National Commission for Scientific and Technological Research, Chile. M.M. Khan was funded by a Federal Ministry of Education and Research grant (German Centre for Lung Research). The authors declare no competing financial interests. Publisher Copyright: {\textcopyright} 2022 Jung et al.",

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doi = "10.1083/jcb.202110081",

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AU - Jung, Juan

AU - Khan, Muzamil Majid

AU - Landry, Jonathan

AU - Halavatyi, Aliaksandr

AU - Machado, Pedro

AU - Reiss, Miriam

AU - Pepperkok, Rainer

N1 - Funding Information: J. Jung was funded by a fellowship from National Commission for Scientific and Technological Research, Chile. M.M. Khan was funded by a Federal Ministry of Education and Research grant (German Centre for Lung Research). The authors declare no competing financial interests. Publisher Copyright: © 2022 Jung et al.

PY - 2022/8/1

Y1 - 2022/8/1

N2 - Proteins that enter the secretory pathway are transported from their place of synthesis in the endoplasmic reticulum to the Golgi complex by COPII-coated carriers. The networks of proteins that regulate these components in response to extracellular cues have remained largely elusive. Using high-throughput microscopy, we comprehensively screened 378 cytoskeletonassociated and related proteins for their functional interaction with the coat protein complex II (COPII) components SEC23A and SEC23B. Among these, we identified a group of proteins associated with focal adhesions (FERMT2, MACF1, MAPK8IP2, NGEF, PIK3CA, and ROCK1) that led to the downregulation of SEC23A when depleted by siRNA. Changes in focal adhesions induced by plating cells on ECM also led to the downregulation of SEC23A and decreases in VSVG transport from ER to Golgi. Both the expression of SEC23A and the transport defect could be rescued by treatment with a focal adhesion kinase inhibitor. Altogether, our results identify a network of cytoskeleton-associated proteins connecting focal adhesions and ECM-related signaling with the gene expression of the COPII secretory machinery and trafficking.

AB - Proteins that enter the secretory pathway are transported from their place of synthesis in the endoplasmic reticulum to the Golgi complex by COPII-coated carriers. The networks of proteins that regulate these components in response to extracellular cues have remained largely elusive. Using high-throughput microscopy, we comprehensively screened 378 cytoskeletonassociated and related proteins for their functional interaction with the coat protein complex II (COPII) components SEC23A and SEC23B. Among these, we identified a group of proteins associated with focal adhesions (FERMT2, MACF1, MAPK8IP2, NGEF, PIK3CA, and ROCK1) that led to the downregulation of SEC23A when depleted by siRNA. Changes in focal adhesions induced by plating cells on ECM also led to the downregulation of SEC23A and decreases in VSVG transport from ER to Golgi. Both the expression of SEC23A and the transport defect could be rescued by treatment with a focal adhesion kinase inhibitor. Altogether, our results identify a network of cytoskeleton-associated proteins connecting focal adhesions and ECM-related signaling with the gene expression of the COPII secretory machinery and trafficking.

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Regulation of the COPII secretory machinery via focal adhesions and extracellular matrix signaling

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