Oct 13, 2017

Multiple pathways facilitate the biogenesis of mammalian tail-anchored proteins

Journal of Cell Science
Joseph CassonStephen High


Tail-anchored (TA) proteins are transmembrane proteins with a single C-terminal transmembrane domain, which functions as both their subcellular targeting signal and membrane anchor. We show that knockout of TRC40 in cultured human cells has a relatively minor effect on endogenous TA proteins, despite their apparent reliance on this pathway in vitro These findings support recent evidence that the canonical TRC40 pathway is not essential for TA protein biogenesis in vivo We therefore investigated the possibility that other ER-targeting routes can complement the TRC40 pathway and identified roles for both the SRP pathway and the recently described mammalian SND pathway in TA protein biogenesis. We conclude that, although TRC40 normally plays an important role in TA protein biogenesis, it is not essential, and speculate that alternative pathways for TA protein biogenesis, including those identified in this study, contribute to the redundancy of the TRC40 pathway.

Mentioned in this Paper

Biochemical Pathway
ASNA1 gene
Carboxy-Terminal Amino Acid
Integral Membrane Proteins
Transmembrane Domain
Sensorineural Hearing Loss (Disorder)
Integral to Membrane
ASNA1 protein, human

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