TY - JOUR
T1 - The signaling pathways underlying starvation-induced upregulation of α-mannosidase Ams1 in Saccharomyces cerevisiae
AU - Umekawa, Midori
AU - Ujihara, Masato
AU - Makishima, Kazuki
AU - Yamamoto, Shohei
AU - Takematsu, Hiromu
AU - Wakayama, Mamoru
N1 - Publisher Copyright:
© 2016 Elsevier B.V. All rights reserved.
PY - 2016/6/1
Y1 - 2016/6/1
N2 - Background Cells have evolved the mechanisms to survive nutritional shortages in the environment. In Saccharomyces cerevisiae, α-mannosidase Ams1 is known to play a role in catabolism of N-linked free oligosaccharides in the cytosol. Although, this enzyme is also known to be transported selectively from the cytosol to the vacuoles by autophagy, the physiological significance of this transport has not been clarified. Methods To elucidate the regulatory mechanism of the activity of Ams1, we assessed the enzymatic activity of the cell free extract of the wild-type and various gene disruptants under different nutritional conditions. In addition, the regulation of Ams1 at both transcription and post-translation was examined. Results The activity of Ams1 was significantly increased upon the depletion of glucose in the medium. Interestingly, the activity of the enzyme was also stimulated by nitrogen starvation. Our data showed that the activity of Ams1 is regulated by the stress responsive transcriptional factors Msn2/4 through the protein kinase A and the target of rapamycin complex 1 pathways. In addition, Ams1 is post-translationally activated by Pep4-dependent processing in the vacuoles. Conclusion Yeast cells monitor extracellular nutrients to regulate mannoside catabolism via the cellular signaling pathway. General significance This study revealed that intracellular Ams1 activity is exquisitely upregulated in response to nutrient starvation by induced expression as well as by Pep4-dependent enhanced activity in the vacuoles. The signaling molecules responsible for regulation of Ams1 were also clarified.
AB - Background Cells have evolved the mechanisms to survive nutritional shortages in the environment. In Saccharomyces cerevisiae, α-mannosidase Ams1 is known to play a role in catabolism of N-linked free oligosaccharides in the cytosol. Although, this enzyme is also known to be transported selectively from the cytosol to the vacuoles by autophagy, the physiological significance of this transport has not been clarified. Methods To elucidate the regulatory mechanism of the activity of Ams1, we assessed the enzymatic activity of the cell free extract of the wild-type and various gene disruptants under different nutritional conditions. In addition, the regulation of Ams1 at both transcription and post-translation was examined. Results The activity of Ams1 was significantly increased upon the depletion of glucose in the medium. Interestingly, the activity of the enzyme was also stimulated by nitrogen starvation. Our data showed that the activity of Ams1 is regulated by the stress responsive transcriptional factors Msn2/4 through the protein kinase A and the target of rapamycin complex 1 pathways. In addition, Ams1 is post-translationally activated by Pep4-dependent processing in the vacuoles. Conclusion Yeast cells monitor extracellular nutrients to regulate mannoside catabolism via the cellular signaling pathway. General significance This study revealed that intracellular Ams1 activity is exquisitely upregulated in response to nutrient starvation by induced expression as well as by Pep4-dependent enhanced activity in the vacuoles. The signaling molecules responsible for regulation of Ams1 were also clarified.
UR - http://www.scopus.com/inward/record.url?scp=84960462048&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84960462048&partnerID=8YFLogxK
U2 - 10.1016/j.bbagen.2016.02.018
DO - 10.1016/j.bbagen.2016.02.018
M3 - Article
C2 - 26947009
AN - SCOPUS:84960462048
SN - 0304-4165
VL - 1860
SP - 1192
EP - 1201
JO - Biochimica et Biophysica Acta - General Subjects
JF - Biochimica et Biophysica Acta - General Subjects
IS - 6
ER -