title: GOLPH3 bridges phosphatidylinositol-4- phosphate and actomyosin to stretch and shape the Golgi to promote budding.
abstract: Golgi membranes, from yeast to humans, are uniquely enriched in phosphatidylinositol-4-phosphate (PtdIns(4)P), although the role of this lipid remains poorly understood. Using a proteomic lipid-binding screen, we identify the Golgi protein GOLPH3 (also called GPP34, GMx33, MIDAS, or yeast Vps74p) as a PtdIns(4)P-binding protein that depends on PtdIns(4)P for its Golgi localization. We further show that GOLPH3 binds the unconventional myosin MYO18A, thus connecting the Golgi to F-actin. We demonstrate that this linkage is necessary for normal Golgi trafficking and morphology. The evidence suggests that GOLPH3 binds to PtdIns(4)P-rich trans-Golgi membranes and MYO18A conveying a tensile force required for efficient tubule and vesicle formation. Consequently, this tensile force stretches the Golgi into the extended ribbon observed by fluorescence microscopy and the familiar flattened form observed by electron microscopy.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, La Jolla, CA 92093-0707, USA.
authors.forename: Holly C
authors.initials: HC
authors.lastname: Dippold
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Ng
authors.forename: Suzette E
authors.initials: SE
authors.lastname: Farber-Katz
authors.forename: Sun-Kyung
authors.initials: SK
authors.lastname: Lee
authors.forename: Monica L
authors.initials: ML
authors.lastname: Kerr
authors.forename: Marshall C
authors.initials: MC
authors.lastname: Peterman
authors.forename: Ronald
authors.initials: R
authors.lastname: Sim
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Wiharto
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Galbraith
authors.forename: Swetha
authors.initials: S
authors.lastname: Madhavarapu
authors.forename: Greg J
authors.initials: GJ
authors.lastname: Fuchs
authors.forename: Timo
authors.initials: T
authors.lastname: Meerloo
authors.forename: Marilyn G
authors.initials: MG
authors.lastname: Farquhar
authors.forename: Huilin
authors.initials: H
authors.lastname: Zhou
authors.forename: Seth J
authors.initials: SJ
authors.lastname: Field
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D055785:Gene Knockdown Techniques; D006056:Golgi Apparatus / Q000737:chemistry / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D009218:Myosins / Q000378:metabolism; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D022161:Transport Vesicles / Q000378:metabolism
chemical_list: D000199:Actins; D008565:Membrane Proteins; D009218:Myosins; D018129:Phosphatidylinositol Phosphates; C429024:GOLPH3 protein, human; C407152:MYO18A protein, human