GOLPH3L antagonizes GOLPH3 to determine Golgi morphology

MM Ng, HC Dippold, MD Buschman… - Molecular biology of …, 2013 - Am Soc Cell Biol
MM Ng, HC Dippold, MD Buschman, CJ Noakes, SJ Field
Molecular biology of the cell, 2013Am Soc Cell Biol
GOLPH3 is a phosphatidylinositol-4-phosphate (PI4P) effector that plays an important role in
maintaining Golgi architecture and anterograde trafficking. GOLPH3 does so through its
ability to link trans-Golgi membranes to F-actin via its interaction with myosin 18A (MYO18A).
GOLPH3 also is known to be an oncogene commonly amplified in human cancers.
GOLPH3L is a GOLPH3 paralogue found in all vertebrate genomes, although previously it
was largely uncharacterized. Here we demonstrate that although GOLPH3 is ubiquitously …
GOLPH3 is a phosphatidylinositol-4-phosphate (PI4P) effector that plays an important role in maintaining Golgi architecture and anterograde trafficking. GOLPH3 does so through its ability to link trans-Golgi membranes to F-actin via its interaction with myosin 18A (MYO18A). GOLPH3 also is known to be an oncogene commonly amplified in human cancers. GOLPH3L is a GOLPH3 paralogue found in all vertebrate genomes, although previously it was largely uncharacterized. Here we demonstrate that although GOLPH3 is ubiquitously expressed in mammalian cells, GOLPH3L is present in only a subset of tissues and cell types, particularly secretory tissues. We show that, like GOLPH3, GOLPH3L binds to PI4P, localizes to the Golgi as a consequence of its PI4P binding, and is required for efficient anterograde trafficking. Surprisingly, however, we find that perturbations of GOLPH3L expression produce effects on Golgi morphology that are opposite to those of GOLPH3 and MYO18A. GOLPH3L differs critically from GOLPH3 in that it is largely unable to bind to MYO18A. Our data demonstrate that despite their similarities, unexpectedly, GOLPH3L antagonizes GOLPH3/MYO18A at the Golgi.
Am Soc Cell Biol