Drosophila arf72A acts as an essential regulator of endoplasmic reticulum quality control and suppresses autosomal-dominant retinopathy
The eukaryotic endoplasmic reticulum operates multiple quality control mechanisms to ensure that only properly folded proteins are exported to their final destinations via the secretory pathway and those that are not are destroyed via the degradation pathway. However, molecular mechanisms underlying...
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Veröffentlicht in: | The international journal of biochemistry & cell biology 2011-09, Vol.43 (9), p.1392-1401 |
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Sprache: | eng |
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Zusammenfassung: | The eukaryotic endoplasmic reticulum operates multiple quality control mechanisms to ensure that only properly folded proteins are exported to their final destinations via the secretory pathway and those that are not are destroyed via the degradation pathway. However, molecular mechanisms underlying such regulated exportation to these distinct routes are unknown. In this article, we report the role of
Drosophila arf72A – the fly homologue of the mammalian
Arl1 – in the quality checks of proteins and in the autosomal-dominant retinopathy. ARF72A localizes to the Golgi membranes of
Drosophila photoreceptor cells, consistent with mammalian
Arl1 localization in cell culture systems. A loss of
arf72A function changes the membrane character of the endoplasmic reticulum and shifts the membrane balance between the endoplasmic reticulum and the Golgi complex toward the Golgi complex, resulting in over-proliferated Golgi complexes and accelerated protein secretion. Interestingly, our study indicated that more ARF72A localized on the endoplasmic reticulum in the
ninaE
D1
photoreceptor cell, a
Drosophila model of autosomal-dominant retinitis pigmentosa, compared to that in the wild-type. In addition,
arf72A loss was shown to rescue the
ninaE
D1
–related membrane accumulation and the rhodopsin maturation defect, and suppress
ninaE
D1
–triggered retinal degeneration, indicating that rhodopsin accumulated in the endoplasmic reticulum bypasses the quality checks. While previous studies of ARF small GTPases have focused on their roles in vesicular budding and transport between the specific organelles, our findings establish an additional function of
arf72A in the quality check machinery of the endoplasmic reticulum distinguishing the cargoes for secretion from those for degradation. |
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ISSN: | 1357-2725 1878-5875 |
DOI: | 10.1016/j.biocel.2011.06.004 |