It has been suggested that a gene termed bubblegum (Bgm), encoding an acyl-CoA synthetase, could be involved in the pathogenesis of the inherited neurodegenerative disorder X-ALD (X-linked adrenoleukodystrophy). The precise function of the ALDP (ALD protein) still remains unclear. Aldp deficiency in mammals and Bgm deficiency in Drosophila led to accumulation of VLCFAs (very long-chain fatty acids). As a first step towards studying this interaction in wild-type versus Aldp-deficient mice, we analysed the expression pattern of the murine orthologue of the Bgm gene. In contrast with the ubiquitously expressed Ald gene, Bgm expression is restricted to the tissues that are affected by X-ALD such as brain, testis and adrenals. During mouse brain development, Bgm mRNA was first detected by Northern-blot analysis on embryonic day 18 and increased steadily towards adulthood, whereas the highest level of Ald mRNA was found on embryonic day 12 and decreased gradually during differentiation. Protein fractionation and confocal laser imaging of Bgm–green fluorescent protein fusion proteins revealed a microsomal localization that was different from peroxisomes (where Aldp is detected), endoplasmic reticulum and Golgi. Mouse Bgm showed acyl-CoA synthetase activity towards a VLCFA substrate in addition to LCFAs, and this activity was enriched in the microsomal compartment. Speculating that Bgm expression could be regulated by Ald deficiency, we compared the abundance of Bgm mRNA in wild-type and Ald knockout mice but observed no difference. Although mouse Bgm is capable of activating VLCFA, we conclude that a direct interaction between the mouse Bgm and the Aldp seems unlikely.
- ABCD1 (ATP-binding cassette
- sub-family D)
- acyl-CoA synthetase
- very long-chain fatty acid
- X-linked adrenoleukodystrophy
Abbreviations used: ACS, acyl-CoA synthetase; Aldp/ALDP, adrenoleukodystrophy protein; EGFP, enhanced green fluorescent protein; ER, endoplasmic reticulum; EST, expressed sequence tag; HRP, horseradish peroxidase; LCFA, long-chain fatty acid; ORF, open reading frame; PDI, protein disulphide isomerase; PTS, peroxisomal targeting signal; RT, reverse transcriptase; uORF, upstream ORF; UTR, untranslated region; VLCFA, very LCFA; VLCS, very long-chain acyl-CoA synthetase; X-ALD, X-linked adrenoleukodystrophy.
- The Biochemical Society, London ©2004