Quality Control in the Yeast Secretory Pathway
Quality Control in the Yeast Secretory Pathway
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酵母分泌途径的质量控制
DOI：
--
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发表时间：
2002
影响因子：
4.8
通讯作者：
C. Slayman
中科院分区：
文献类型：
--
作者：
T. Ferreira;A. Mason;M. Pypaert;K. Allen;C. Slayman
由PMA 1编码的酵母质膜H+-ATP酶通过分泌途径传递到细胞表面，并且最近已经成为用于沿着该途径鉴定质量控制机制的优秀系统。在本研究中，我们跟踪了Pma 1-G381 A，一个错误折叠的突变形式的H+-ATP酶的生物起源。虽然这种突变的ATP酶在外周内质网中被短暂地阻止，但它不会成为内质网相关降解的底物，也不会刺激未折叠的蛋白质反应。相反，Pma 1-G381 A在含有Kar 2 p的囊泡-管状簇中积累，这类似于先前在哺乳动物细胞中描述的那些。与哺乳动物类似，酵母囊泡-管状簇可能对应于内质网的特定出口，因为Pma 1-G381 A最终从它们中逃逸（仍然以错误折叠的胰蛋白酶敏感形式）到达质膜。与野生型ATP酶相比，Pma 1-G381 A在质膜上的半衰期很短，然后被去除并送到液泡中降解，这一过程需要End 4p和Pep 4p。最后，在一组单独的实验中，发现Pma 1-G381 A将其表型强加于共表达的野生型ATP酶上，瞬时阻滞ER中的野生型蛋白质，随后刺激其在液泡中的降解。这两种效应都有助于降低质膜中野生型ATP酶的稳态量，因此可以解释G381 A突变的共显性遗传行为。综上所述，本研究的结果建立Pma 1-G381 A作为一个有用的新的酵母分泌系统的探针。
The yeast plasma-membrane H+-ATPase, encoded by PMA1, is delivered to the cell surface via the secretory pathway and has recently emerged as an excellent system for identifying quality control mechanisms along the pathway. In the present study, we have tracked the biogenesis of Pma1-G381A, a misfolded mutant form of the H+-ATPase. Although this mutant ATPase is arrested transiently in the peripheral endoplasmic reticulum, it does not become a substrate for endoplasmic reticulum-associated degradation nor does it appear to stimulate an unfolded protein response. Instead, Pma1-G381A accumulates in Kar2p-containing vesicular-tubular clusters that resemble those previously described in mammalian cells. Like their mammalian counterparts, the yeast vesicular-tubular clusters may correspond to specific exit ports from the endoplasmic reticulum, since Pma1-G381A eventually escapes from them (still in a misfolded, trypsin-sensitive form) to reach the plasma membrane. By comparison with wild-type ATPase, Pma1-G381A spends a short half-life at the plasma membrane before being removed and sent to the vacuole for degradation in a process that requires both End4p and Pep4p. Finally, in a separate set of experiments, Pma1-G381A was found to impose its phenotype on co-expressed wild-type ATPase, transiently retarding the wild-type protein in the ER and later stimulating its degradation in the vacuole. Both effects serve to lower the steady-state amount of wild-type ATPase in the plasma membrane and, thus, can explain the co-dominant genetic behavior of the G381A mutation. Taken together, the results of this study establish Pma1-G381A as a useful new probe for the yeast secretory system.
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影响因子：
2.9
作者：
LUTSENKO, S;KAPLAN, JH
通讯作者：
KAPLAN, JH
SEC53 的产物是酵母内质网腔中分泌蛋白的折叠和糖基化所必需的。
DOI：
--
发表时间：
1987
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Feldman,RI;Bernstein,M;Schekman,R
通讯作者：
Schekman,R
分泌囊泡中酵母质膜[H]ATP酶的表达。
DOI：
--
发表时间：
1991
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Nakamoto,RK;Rao,R;Slayman,CW
通讯作者：
Slayman,CW
从酿酒酵母中分离具有运输能力的分泌囊泡。
DOI：
10.1006/abio.1997.2257
发表时间：
1997
期刊：
Analytical biochemistry.
影响因子：
--
作者：
Ambesi,A;Allen,KE;Slayman,CW
通讯作者：
Slayman,CW
CFTR 的生物合成和降解。
DOI：
10.1152/physrev.1999.79.1.s167
发表时间：
1999
期刊：
Physiological reviews.
影响因子：
--
作者：
Kopito,RR
通讯作者：
Kopito,RR