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Cell-matrix adhesion controls Golgi organization and function by regulating Arf1 activation in anchorage dependent cells

View ORCID ProfileVibha Singh, View ORCID ProfileChaitanya Erady, View ORCID ProfileNagaraj Balasubramanian
doi: https://doi.org/10.1101/261842
Vibha Singh
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Chaitanya Erady
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Nagaraj Balasubramanian
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Abstract

Cell-matrix adhesion regulates membrane trafficking to control anchorage-dependent signaling. While a dynamic Golgi complex can contribute to this pathway, its control by adhesion remains untested. We find the loss of adhesion rapidly disorganizes the Golgi in mouse and human fibroblast cells, its integrity restored rapidly on re-adhesion to fibronectin (but not poly-l-lysine coated beads) along the microtubule network. Adhesion regulates the trans-Golgi more prominently than the cis /cis-medial Golgi, though they show no fallback into the ER making this reorganization distinct from known Golgi fragmentation. This is controlled by an adhesion-dependent drop and recovery of Arf1 activation, mediated through the Arf1 GEF BIG1/2 over GBF1. Constitutively active Arf1 disrupts this regulation and prevents Golgi disorganization in non-adherent cells. Adhesion regulates active Arf1 binding to the microtubule minus-end motor protein dynein to control Golgi reorganization, which ciliobrevin blocks. This regulation by adhesion controls Golgi function, promoting cell surface glycosylation on the loss of adhesion that constitutively active Arf1 blocks. This study hence identifies cell-matrix adhesion to be a novel regulator of Arf1 activation, controlling Golgi organization and function in anchorage-dependent cells.

Summary Statement This study identifies a role for cell-matrix adhesion in regulating organelle (Golgi) architecture and function which could have implications for multiple cellular pathways and function.

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Posted February 09, 2018.
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Cell-matrix adhesion controls Golgi organization and function by regulating Arf1 activation in anchorage dependent cells
Vibha Singh, Chaitanya Erady, Nagaraj Balasubramanian
bioRxiv 261842; doi: https://doi.org/10.1101/261842
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Cell-matrix adhesion controls Golgi organization and function by regulating Arf1 activation in anchorage dependent cells
Vibha Singh, Chaitanya Erady, Nagaraj Balasubramanian
bioRxiv 261842; doi: https://doi.org/10.1101/261842

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