Dissecting the function of Atg1 complex in Dictyostelium autophagy reveals a connection with the pentose phosphate pathway enzyme transketolase
The network of protein–protein interactions of the Dictyostelium discoideum autophagy pathway was investigated by yeast two-hybrid screening of the conserved autophagic proteins Atg1 and Atg8. These analyses confirmed expected interactions described in other organisms and also identified novel inter...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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The Royal Society
2015-01-01
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| Series: | Open Biology |
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| Online Access: | https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.150088 |
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| author | Ana Mesquita Luis C. Tábara Oscar Martinez-Costa Natalia Santos-Rodrigo Olivier Vincent Ricardo Escalante |
| author_facet | Ana Mesquita Luis C. Tábara Oscar Martinez-Costa Natalia Santos-Rodrigo Olivier Vincent Ricardo Escalante |
| author_sort | Ana Mesquita |
| collection | DOAJ |
| description | The network of protein–protein interactions of the Dictyostelium discoideum autophagy pathway was investigated by yeast two-hybrid screening of the conserved autophagic proteins Atg1 and Atg8. These analyses confirmed expected interactions described in other organisms and also identified novel interactors that highlight the complexity of autophagy regulation. The Atg1 kinase complex, an essential regulator of autophagy, was investigated in detail here. The composition of the Atg1 complex in D. discoideum is more similar to mammalian cells than to Saccharomyces cerevisiae as, besides Atg13, it contains Atg101, a protein not conserved in this yeast. We found that Atg101 interacts with Atg13 and genetic disruption of these proteins in Dictyostelium leads to an early block in autophagy, although the severity of the developmental phenotype and the degree of autophagic block is higher in Atg13-deficient cells. We have also identified a protein containing zinc-finger B-box and FNIP motifs that interacts with Atg101. Disruption of this protein increases autophagic flux, suggesting that it functions as a negative regulator of Atg101. We also describe the interaction of Atg1 kinase with the pentose phosphate pathway enzyme transketolase (TKT). We found changes in the activity of endogenous TKT activity in strains lacking or overexpressing Atg1, suggesting the presence of an unsuspected regulatory pathway between autophagy and the pentose phosphate pathway in Dictyostelium that seems to be conserved in mammalian cells. |
| first_indexed | 2024-12-21T05:28:45Z |
| format | Article |
| id | doaj.art-9e2a9fea97b54f7dae6fb7f60b0a01b2 |
| institution | Directory Open Access Journal |
| issn | 2046-2441 |
| language | English |
| last_indexed | 2024-12-21T05:28:45Z |
| publishDate | 2015-01-01 |
| publisher | The Royal Society |
| record_format | Article |
| series | Open Biology |
| spelling | doaj.art-9e2a9fea97b54f7dae6fb7f60b0a01b22022-12-21T19:14:35ZengThe Royal SocietyOpen Biology2046-24412015-01-015810.1098/rsob.150088150088Dissecting the function of Atg1 complex in Dictyostelium autophagy reveals a connection with the pentose phosphate pathway enzyme transketolaseAna MesquitaLuis C. TábaraOscar Martinez-CostaNatalia Santos-RodrigoOlivier VincentRicardo EscalanteThe network of protein–protein interactions of the Dictyostelium discoideum autophagy pathway was investigated by yeast two-hybrid screening of the conserved autophagic proteins Atg1 and Atg8. These analyses confirmed expected interactions described in other organisms and also identified novel interactors that highlight the complexity of autophagy regulation. The Atg1 kinase complex, an essential regulator of autophagy, was investigated in detail here. The composition of the Atg1 complex in D. discoideum is more similar to mammalian cells than to Saccharomyces cerevisiae as, besides Atg13, it contains Atg101, a protein not conserved in this yeast. We found that Atg101 interacts with Atg13 and genetic disruption of these proteins in Dictyostelium leads to an early block in autophagy, although the severity of the developmental phenotype and the degree of autophagic block is higher in Atg13-deficient cells. We have also identified a protein containing zinc-finger B-box and FNIP motifs that interacts with Atg101. Disruption of this protein increases autophagic flux, suggesting that it functions as a negative regulator of Atg101. We also describe the interaction of Atg1 kinase with the pentose phosphate pathway enzyme transketolase (TKT). We found changes in the activity of endogenous TKT activity in strains lacking or overexpressing Atg1, suggesting the presence of an unsuspected regulatory pathway between autophagy and the pentose phosphate pathway in Dictyostelium that seems to be conserved in mammalian cells.https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.150088dictyosteliumautophagyatg1 complexatg8atg101transketolase |
| spellingShingle | Ana Mesquita Luis C. Tábara Oscar Martinez-Costa Natalia Santos-Rodrigo Olivier Vincent Ricardo Escalante Dissecting the function of Atg1 complex in Dictyostelium autophagy reveals a connection with the pentose phosphate pathway enzyme transketolase Open Biology dictyostelium autophagy atg1 complex atg8 atg101 transketolase |
| title | Dissecting the function of Atg1 complex in Dictyostelium autophagy reveals a connection with the pentose phosphate pathway enzyme transketolase |
| title_full | Dissecting the function of Atg1 complex in Dictyostelium autophagy reveals a connection with the pentose phosphate pathway enzyme transketolase |
| title_fullStr | Dissecting the function of Atg1 complex in Dictyostelium autophagy reveals a connection with the pentose phosphate pathway enzyme transketolase |
| title_full_unstemmed | Dissecting the function of Atg1 complex in Dictyostelium autophagy reveals a connection with the pentose phosphate pathway enzyme transketolase |
| title_short | Dissecting the function of Atg1 complex in Dictyostelium autophagy reveals a connection with the pentose phosphate pathway enzyme transketolase |
| title_sort | dissecting the function of atg1 complex in dictyostelium autophagy reveals a connection with the pentose phosphate pathway enzyme transketolase |
| topic | dictyostelium autophagy atg1 complex atg8 atg101 transketolase |
| url | https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.150088 |
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