GOLPH3 bridges phosphatidylinositol-4- phosphate and actomyosin to stretch and shape the Golgi to promote budding.
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.
Dippold
Holly C
HC
Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, La Jolla, CA 92093-0707, USA.
Ng
Michelle M
MM
Farber-Katz
Suzette E
SE
Lee
Sun-Kyung
SK
Kerr
Monica L
ML
Peterman
Marshall C
MC
Sim
Ronald
R
Wiharto
Patricia A
PA
Galbraith
Kenneth A
KA
Madhavarapu
Swetha
S
Fuchs
Greg J
GJ
Meerloo
Timo
T
Farquhar
Marilyn G
MG
Zhou
Huilin
H
Field
Seth J
SJ
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
D000199:Actins; D008565:Membrane Proteins; D009218:Myosins; D018129:Phosphatidylinositol Phosphates; C429024:GOLPH3 protein, human; C407152:MYO18A protein, human