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α–SNAP inhibits AMPK signaling to reduce mitochondrial biogenesis and dephosphorylates Thr172 in AMPKα in vitro
The AMP-activated protein kinase (AMPK) regulates metabolism in normal and pathological conditions and responds to nutrients, hormones, anti-diabetic drugs and physical exercise. AMPK is activated by kinase LKB1 and inactivated by phosphatases whose identities remain uncertain. Here we show that AMP...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2013
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3595137/ https://www.ncbi.nlm.nih.gov/pubmed/23463002 http://dx.doi.org/10.1038/ncomms2565 |
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author | Wang, Lifu Brautigan, David L. |
author_facet | Wang, Lifu Brautigan, David L. |
author_sort | Wang, Lifu |
collection | PubMed |
description | The AMP-activated protein kinase (AMPK) regulates metabolism in normal and pathological conditions and responds to nutrients, hormones, anti-diabetic drugs and physical exercise. AMPK is activated by kinase LKB1 and inactivated by phosphatases whose identities remain uncertain. Here we show that AMPK associates with α-SNAP, an adapter that enables disassembly of cis-SNARE complexes formed during membrane fusion. Knockdown of α-SNAP activates AMPK to phosphorylate its endogenous substrates ACC and Raptor and provokes mitochondrial biogenesis. AMPK phosphorylation is rescued from α-SNAP RNAi by LKB1 knockdown or expression of wild type but not mutated α-SNAP. Recombinant wild type but not mutated α-SNAP dephosphorylates pThr172 in AMPKα in vitro. Over-expression of wild-type but not mutated α-SNAP prevents AMPK activation in cells treated with agents to elevate AMP concentration. The mouse α-SNAP mutant hyh (hydrocephalus with hop gait) shows enhanced binding and inhibition of AMPK. By negatively controlling AMPK, α-SNAP therefore potentially coordinates membrane trafficking and metabolism. |
format | Online Article Text |
id | pubmed-3595137 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
record_format | MEDLINE/PubMed |
spelling | pubmed-35951372013-09-05 α–SNAP inhibits AMPK signaling to reduce mitochondrial biogenesis and dephosphorylates Thr172 in AMPKα in vitro Wang, Lifu Brautigan, David L. Nat Commun Article The AMP-activated protein kinase (AMPK) regulates metabolism in normal and pathological conditions and responds to nutrients, hormones, anti-diabetic drugs and physical exercise. AMPK is activated by kinase LKB1 and inactivated by phosphatases whose identities remain uncertain. Here we show that AMPK associates with α-SNAP, an adapter that enables disassembly of cis-SNARE complexes formed during membrane fusion. Knockdown of α-SNAP activates AMPK to phosphorylate its endogenous substrates ACC and Raptor and provokes mitochondrial biogenesis. AMPK phosphorylation is rescued from α-SNAP RNAi by LKB1 knockdown or expression of wild type but not mutated α-SNAP. Recombinant wild type but not mutated α-SNAP dephosphorylates pThr172 in AMPKα in vitro. Over-expression of wild-type but not mutated α-SNAP prevents AMPK activation in cells treated with agents to elevate AMP concentration. The mouse α-SNAP mutant hyh (hydrocephalus with hop gait) shows enhanced binding and inhibition of AMPK. By negatively controlling AMPK, α-SNAP therefore potentially coordinates membrane trafficking and metabolism. 2013 /pmc/articles/PMC3595137/ /pubmed/23463002 http://dx.doi.org/10.1038/ncomms2565 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Wang, Lifu Brautigan, David L. α–SNAP inhibits AMPK signaling to reduce mitochondrial biogenesis and dephosphorylates Thr172 in AMPKα in vitro |
title | α–SNAP inhibits AMPK signaling to reduce mitochondrial biogenesis and dephosphorylates Thr172 in AMPKα in vitro |
title_full | α–SNAP inhibits AMPK signaling to reduce mitochondrial biogenesis and dephosphorylates Thr172 in AMPKα in vitro |
title_fullStr | α–SNAP inhibits AMPK signaling to reduce mitochondrial biogenesis and dephosphorylates Thr172 in AMPKα in vitro |
title_full_unstemmed | α–SNAP inhibits AMPK signaling to reduce mitochondrial biogenesis and dephosphorylates Thr172 in AMPKα in vitro |
title_short | α–SNAP inhibits AMPK signaling to reduce mitochondrial biogenesis and dephosphorylates Thr172 in AMPKα in vitro |
title_sort | α–snap inhibits ampk signaling to reduce mitochondrial biogenesis and dephosphorylates thr172 in ampkα in vitro |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3595137/ https://www.ncbi.nlm.nih.gov/pubmed/23463002 http://dx.doi.org/10.1038/ncomms2565 |
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