Unconventional secretion of Acb1 is mediated by autophagosomes.

Evidence is presented for an unconventional protein secretion pathway that is conserved from yeast to Dictyostelium discoideum in which Acb1 may be sequestered into autophagosomal vesicles, which then fuse (either directly or indirectly) with the plasma membrane (see also the companion paper from Manjithaya et al. in this issue). Starving Dictyostelium discoideum cells secrete AcbA, an acyl coenzyme A–binding protein (ACBP) that lacks a conventional signal sequence for entering the endoplasmic reticulum (ER). Secretion of AcbA in D. discoideum requires the Golgi-associated protein GRASP. In this study, we report that starvation-induced secretion of Acb1, the Saccharomyces cerevisiae ACBP orthologue, also requires GRASP (Grh1). This highlights the conserved function of GRASP in unconventional secretion. Although genes required for ER to Golgi or Golgi to cell surface transport are not required for Acb1 secretion in yeast, this process involves autophagy genes and the plasma membrane t-SNARE, Sso1. Inhibiting transport to vacuoles does not affect Acb1 secretion. In sum, our experiments reveal a unique secretory pathway where autophagosomes containing Acb1 evade fusion with the vacuole to prevent cargo degradation. We propose that these autophagosome intermediates fuse with recycling endosomes instead to form multivesicular body carriers that then fuse with the plasma membrane to release cargo.

有证据表明存在一种从酵母到盘基网柄菌都保守的非常规蛋白质分泌途径，在该途径中，Acb1可能被隔离到自噬体小泡中，然后（直接或间接）与质膜融合（也可参见本期Manjithaya等人的相关论文）。 饥饿的盘基网柄菌细胞会分泌AcbA，这是一种酰基辅酶A结合蛋白（ACBP），它缺乏进入内质网（ER）的常规信号序列。盘基网柄菌中AcbA的分泌需要高尔基体相关蛋白GRASP。在本研究中，我们报道饥饿诱导的酿酒酵母ACBP同源物Acb1的分泌也需要GRASP（Grh1）。这凸显了GRASP在非常规分泌中的保守功能。尽管酵母中Acb1的分泌不需要内质网到高尔基体或高尔基体到细胞表面运输所需的基因，但这个过程涉及自噬基因和质膜t - SNARE（可溶性N - 乙基马来酰亚胺敏感因子附着蛋白受体）Sso1。抑制向液泡的运输并不影响Acb1的分泌。总之，我们的实验揭示了一种独特的分泌途径，其中含有Acb1的自噬体避免与液泡融合以防止货物降解。我们提出这些自噬体中间产物与再循环内体融合，形成多囊泡体载体，然后与质膜融合以释放货物。