γ-Adducin promotes process outgrowth and secretory protein exit from the Golgi apparatus.
α, β, and γ adducins mediate F-actin remodeling of plasma membrane structures as heterotetramers. Here, we present two new functions of γ-adducin. (1) Overexpression of γ-adducin promoted formation of neurite-like processes in non-neuronal fibroblast COS7 cells. Conversely, overexpression of the C-terminal 38 amino acids of γ-adducin (γAdd(C38)) acting as a dominant negative inhibited formation of neurites/processes in Neuro2A cells and anterior pituitary AtT20 cells. (2) γ-Adducin appears to facilitate pro-opiomelanocortin (POMC) exit from the trans-Golgi network (TGN) by re-organizing the actin network around the Golgi complex. Filamentous actins (F-actins) which formed puncti around the Golgi complex in control cells were dispersed in AtT20 cells stably transfected with γAdd(C38). Furthermore, γAdd(C38)-transfectants showed significant accumulation of POMC/adrenocorticotropin (ACTH) in the Golgi complex and diminished POMC/ACTH vesicles in the cell processes. The C-terminal 38 amino acids of γ-adducin interacted with F-actins around the Golgi complex, to facilitate F-actin-mediated budding of POMC/ACTH vesicles from the TGN. Thus, we propose that γ-adducin, via its interaction with F-actins, plays a critical role in actin remodeling to facilitate process/neurite outgrowth, as well as budding of POMC/ACTH vesicles from the TGN via its interaction with peri-Golgi F-actins.
Section on Cellular Neurobiology, Program on Developmental Neuroscience, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bldg 49, Rm 5A22, 49 Convent Drive, Bethesda, MD 20892, USA.
Hong
H
Lou
Joshua J
JJ
Park
Andre
A
Phillips
Y Peng
YP
Loh
D000199:Actins / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002148:Calmodulin-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D049108:Cell Enlargement; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D003598:Cytoskeletal Proteins; D006056:Golgi Apparatus / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D016501:Neurites / Q000378:metabolism / Q000502:physiology; D011333:Pro-Opiomelanocortin / Q000378:metabolism*; D054730:Protein Interaction Domains and Motifs; D021381:Protein Transport; D055571:Secretory Pathway; D022142:Secretory Vesicles / Q000378:metabolism; D021601:trans-Golgi Network / Q000378:metabolism; D000099291:Adducins
D000199:Actins; D000324:Adrenocorticotropic Hormone; D002148:Calmodulin-Binding Proteins; D003598:Cytoskeletal Proteins; D011333:Pro-Opiomelanocortin; D000099291:Adducins; C581599:Add3 protein, mouse