Regulation of Golgi structure and function by ARF-like protein 1 (Arl1).
Arl1 is a member of the ARF-like protein (Arl) subfamily of small GTPases. Nothing is known about the function of Arl1 except for the fact that it is essential for normal development in Drosophila and that it is associated with the Golgi apparatus. In this study, we first demonstrate that Arl1 is enriched at the trans side of the Golgi, marked by AP-1. Association of Arl1 with the Golgi is saturable in intact cells and depends on N-terminal myristoylation. Over-expression of Arl1(T31N), which is expected to be restricted to the GDP-bound form and thus function as a dominant-negative mutant, causes the disappearance of the Golgi apparatus (marked by Golgi SNARE GS28), suggesting that Arl1 is necessary for maintaining normal Golgi structure. Overexpression of Arl1(Q71L), a mutant restricted primarily to the activated GTP-bound form, causes an expansion of the Golgi apparatus with massive and stable Golgi association of COPI and AP-1 coats. Interestingly, Golgi ARFs also become stably associated with the expanded Golgi. Transport of the envelope protein of vesicular stomatitis virus (VSV-G) along the secretory pathway is arrested at the expanded Golgi upon expression of Arl1(Q71L). The structure of stacked cisternae of the Golgi is disrupted in cells expressing Arl1(Q71L), resulting in the transformation of the Golgi into an extensive vesicule-tubule network. In addition, the GTP form of Arl1 interacts with arfaptin-2/POR1 but not GGA1, both of which interact with GTP-restricted ARF1, suggesting that Arl1 and ARF1 share some common effectors in regulating cellular events. On the basis of these observations, we propose that one of the mechanisms for the cell to regulate the structure and function of the Golgi apparatus is through the action of Arl1.
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Membrane Biology Laboratory, Institute of Molecular and Cell Biology, Singapore.
Horstmann
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Ng
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Hong
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D020727:ADP-Ribosylation Factors / Q000378:metabolism; D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D016466:CHO Cells; D002352:Carrier Proteins / Q000378:metabolism; D020755:Coat Protein Complex I / Q000378:metabolism; D006224:Cricetinae; D004789:Enzyme Activation / Q000235:genetics; D020558:GTP Phosphohydrolases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005973:Glutamine / Q000235:genetics; D006056:Golgi Apparatus / Q000235:genetics / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure; D006153:Guanosine Diphosphate / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007930:Leucine / Q000235:genetics; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016253:Microscopy, Immunoelectron; D016297:Mutagenesis, Site-Directed; D019814:Myristic Acid / Q000378:metabolism; D021381:Protein Transport / Q000235:genetics; D051381:Rats; D014162:Transfection; D014407:Tumor Cells, Cultured; D021601:trans-Golgi Network / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure
D033942:Adaptor Proteins, Vesicular Transport; D002352:Carrier Proteins; D020755:Coat Protein Complex I; D008565:Membrane Proteins; D019814:Myristic Acid; D005973:Glutamine; D006153:Guanosine Diphosphate; C097313:ADP-ribosylation factor related proteins; D020558:GTP Phosphohydrolases; D020727:ADP-Ribosylation Factors; D007930:Leucine