Cohen Michael J, Philippe Brianne, Lipke Peter N
Biology Department, Brooklyn College of the City University of New York, Brooklyn, NY 11210, USA.
The Graduate Center of the City University of New York, New York, NY 10016, USA.
Cell Surf. 2024 Dec 24;13:100138. doi: 10.1016/j.tcsw.2024.100138. eCollection 2025 Jun.
Yeast cell walls contain both classically-secreted and unconventionally-secreted proteins. The latter class lacks the signal sequence for translocation into the ER, therefore these proteins are transported to the wall by uncharacterized mechanisms. One such protein is the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) which is abundant in the cytosol, but also found in the yeast cell wall where it is enzymatically active. We screened diploid homozygous gene deletions for changes in cell wall GAPDH activity. Deletions targeting endocytic tethers in the endolysosomal system had the largest effects on GAPDH secretion, including . The predominant GAPDH isoform Tdh3 was partially localized to endolysosomal compartments, including multivesicular bodies, which are common entry points to unconventional protein secretion pathways. Yeast lacking the endosomal Rab5-GTPase Vps21 had defects in GAPDH secretion as well as delayed entry into to the endolysosomal compartments. Therefore, we conclude that entry into the endolysosomal compartment facilitates non-conventional secretion of GAPDH.
酵母细胞壁包含经典分泌蛋白和非经典分泌蛋白。后者缺乏转运至内质网的信号序列，因此这些蛋白通过未知机制运输至细胞壁。其中一种蛋白是糖酵解酶甘油醛-3-磷酸脱氢酶（GAPDH），它在细胞质中含量丰富，但在酵母细胞壁中也有发现且具有酶活性。我们筛选了二倍体纯合基因缺失株，以研究细胞壁GAPDH活性的变化。靶向内溶酶体系统中内吞栓系蛋白的缺失对GAPDH分泌影响最大，包括……主要的GAPDH同工型Tdh3部分定位于内溶酶体区室，包括多囊泡体，而多囊泡体是非常规蛋白质分泌途径的常见入口点。缺乏内体Rab5-GTP酶Vps21的酵母在GAPDH分泌方面存在缺陷，且进入内溶酶体区室的过程延迟。因此，我们得出结论，进入内溶酶体区室有助于GAPDH的非常规分泌。
