Various proteins are now known to be transported to the cell surface or are secreted independently of the canonical ER–Golgi pathway. Some examples of such cargoes that are transported in the vesicular mode are acyl-CoA binding protein, cystic fibrosis transmembrane conductance regulator (CFTR), and some of the interleukins. For this form of conserved mechanism of unconventional secretion, there is an emerging role for autophagy and the Golgi-associated protein GRASP. Biogenesis of such unconventional vesicles, as shown in a recent study in yeast, occurs at unique regions near ER exit sites known as CUPS (compartments for unconventional protein secretion). CUPS are devoid of Golgi or endosomal proteins but harbor GRASP, proteins implicated in autophagy and the ESCRT process. However, the molecular details regarding the nature of these vesicles and what sets them apart from a typical autophagosomal fate have not been elucidated. Future work should reveal additional components that impart cargo and destination selectivity to these vesicles, and identify critical modulators of this understated unconventional secretory pathway.
Various proteins are now known to be transported to the cell surface or are secreted independently of the canonical ER–Golgi pathway. Some examples of such cargoes that are transported in the vesicular mode are acyl-CoA binding protein, cystic fibrosis transmembrane conductance regulator (CFTR), and some of the interleukins. For this form of conserved mechanism of unconventional secretion, there is an emerging role for autophagy and the Golgi-associated protein GRASP. Biogenesis of such unconventional vesicles, as shown in a recent study in yeast, occurs at unique regions near ER exit sites known as CUPS (compartments for unconventional protein secretion). CUPS are devoid of Golgi or endosomal proteins but harbor GRASP, proteins implicated in autophagy and the ESCRT process. However, the molecular details regarding the nature of these vesicles and what sets them apart from a typical autophagosomal fate have not been elucidated. Future work should reveal additional components that impart cargo and destination selectivity to these vesicles, and identify critical modulators of this understated unconventional secretory pathway.
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