MAP1B-LC1 prevents autophagosome formation by linking syntaxin 17 to microtubules.
Kohei ArasakiHaruki NagashimaYuri KurosawaHana KimuraNaoki NishidaNaoshi DohmaeAkitsugu YamamotoShigeru YanagiYuichi WakanaHiroki InoueMitsuo TagayaPublished in: EMBO reports (2018)
In fed cells, syntaxin 17 (Stx17) is associated with microtubules at the endoplasmic reticulum-mitochondria interface and promotes mitochondrial fission by determining the localization and function of the mitochondrial fission factor Drp1. Upon starvation, Stx17 dissociates from microtubules and Drp1, and binds to Atg14L, a subunit of the phosphatidylinositol 3-kinase complex, to facilitate phosphatidylinositol 3-phosphate production and thereby autophagosome formation, but the mechanism underlying this phenomenon remains unknown. Here we identify MAP1B-LC1 (microtubule-associated protein 1B-light chain 1) as a critical regulator of Stx17 function. Depletion of MAP1B-LC1 causes Stx17-dependent autophagosome accumulation even under nutrient-rich conditions, whereas its overexpression blocks starvation-induced autophagosome formation. MAP1B-LC1 links microtubules and Stx17 in fed cells, and starvation causes the dephosphorylation of MAP1B-LC1 at Thr217, allowing Stx17 to dissociate from MAP1B-LC1 and bind to Atg14L. Our results reveal the mechanism by which Stx17 changes its binding partners in response to nutrient status.
Keyphrases
- simultaneous determination
- induced apoptosis
- endoplasmic reticulum
- high density
- mass spectrometry
- cell cycle arrest
- oxidative stress
- liquid chromatography
- protein kinase
- cell death
- transcription factor
- gene expression
- solid phase extraction
- reactive oxygen species
- high glucose
- tyrosine kinase
- hiv testing
- high resolution mass spectrometry
- stress induced
- high resolution
- binding protein
- men who have sex with men