The GOLPH3 pathway regulates Golgi shape and function and is activated by DNA damage.

Matthew D Buschman,Seth J Field,Mengke Xing

doi:10.3389/fnins.2015.00362

Matthew D Buschman, Seth J Field + Show 1 more

Open Access

https://doi.org/10.3389/fnins.2015.00362

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Abstract

The Golgi protein GOLPH3 binds to PtdIns(4)P and MYO18A, linking the Golgi to the actin cytoskeleton. The GOLPH3 pathway is essential for vesicular trafficking from the Golgi to the plasma membrane. A side effect of GOLPH3-dependent trafficking is to generate the extended ribbon shape of the Golgi. Perturbation of the pathway results in changes to both Golgi morphology and secretion, with functional consequences for the cell. The cellular response to DNA damage provides an example of GOLPH3-mediated regulation of the Golgi. Upon DNA damage, DNA-PK phosphorylation of GOLPH3 increases binding to MYO18A, activating the GOLPH3 pathway, which consequently results in Golgi fragmentation, reduced trafficking, and enhanced cell survival. The PtdIns(4)P/GOLPH3/MYO18A/F-actin pathway provides new insight into the relationship between Golgi morphology and function, and their regulation.

Highlights

In many mammalian cell types the Golgi complex appears by light microscopy as an extended ribbon that wraps partially around the nucleus
We have demonstrated that the GOLPH3-dependent Golgi response to DNA damage is functionally important for cell survival after DNA damage
Our discovery that the Golgi is regulated in response to DNA damage via DNA-PK activation of the GOLPH3 pathway provides a plausible link between the evidence implicating DNA damage and altered Golgi function in neurodegenerative disease

Summary

Introduction

In many mammalian cell types the Golgi complex appears by light microscopy as an extended ribbon that wraps partially around the nucleus. Perturbations of the GOLPH3 Pathway Alter Trafficking and Golgi Morphology All of the components of the pathway, PtdIns(4)P, GOLPH3, MYO18A, and F-actin, are required for efficient Golgi-to-plasma membrane trafficking. Depletion of PtdIns(4)P, GOLPH3, MYO18A, or F-actin results in both a defect in Golgi-to-plasma membrane trafficking and a striking change in the morphology of the Golgi (Figure 2).

Results

Conclusion