ARL4, an ARF-like protein that is developmentally regulated and localized to nuclei and nucleoli

Ching Yi Lin, Pei Hsin Huang, Wei Li Liao, Hwai-Jong Cheng, Chun Fang Huang, Jer Cheng Kuo, Walter A. Patton, Donald Massenburg, Joel Moss, Fang Jen S Lee

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

ADP-ribosylation factors (ARFs) are highly conserved ~20-kDa guanine nucleotide-binding proteins that participate in both exocytic and endocytic vesicular transport pathways via mechanisms that are only partially understood. Although several ARF-like proteins (ARLs) are known, their biological functions remain unclear. To characterize its molecular properties, we cloned mouse and human ARL4 (mARL4 and hARL4) cDNA. The appearance of mouse ARL4 mRNA during embryonic development coincided temporally with the sequential formation of somites and the establishment of brain compartmentation. Using ARL4-specific antibody for immunofluorescence microscopy, we observed that endogenous mARL4 in cultured Sertoli and neuroblastoma cells was mainly concentrated in nuclei. When expressed in COS7 cells, ARL4-T34N mutant, predicted to exist with GDP bound, was concentrated in nucleoli. Yeast two-hybrid screening and in vitro protein-interaction assays showed that hARL4 interacted with importin-α through its C-terminal NLS region and that the interaction was not nucleotide-dependent. Like ARL2 and -3, recombinant hARL4 did not enhance cholera toxin-catalyzed auto-ADP-ribosylation. Its binding of guanosine 5'-O-(thiotriphosphate) was modified by phospholipid and detergent, and the N terminus of hARL4, like that of ARF, was myristoylated. Our findings suggest that ARL4, with its distinctive nuclear/nucleolar localization and pattern of developmental expression, may play a unique role(s) in neurogenesis and somitogenesis during embryonic development and in the early stages of spermatogenesis in adults.

Original languageEnglish (US)
Pages (from-to)37815-37823
Number of pages9
JournalJournal of Biological Chemistry
Volume275
Issue number48
DOIs
StatePublished - Dec 1 2000
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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    Lin, C. Y., Huang, P. H., Liao, W. L., Cheng, H-J., Huang, C. F., Kuo, J. C., Patton, W. A., Massenburg, D., Moss, J., & Lee, F. J. S. (2000). ARL4, an ARF-like protein that is developmentally regulated and localized to nuclei and nucleoli. Journal of Biological Chemistry, 275(48), 37815-37823. https://doi.org/10.1074/jbc.M002470200