MAP1B-LC1 prevents autophagosome formation by linking syntaxin 17 to microtubules

作者：Arasaki Kohei^*; Nagashima Haruki; Kurosawa Yuri; Kimura Hana; Nishida Naoki; Dohmae Naoshi; Yamamoto Akitsugu; Yanagi Shigeru; Wakana Yuichi; Inoue Hiroki; Tagaya Mitsuo^*

来源：EMBO Reports, 2018, 19(8): UNSP e45584.

DOI：10.15252/embr.201745584

• Atg14L
• autophagy
• MAP1B-LC1
• microtubules
• syntaxin 17

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.

• 出版日期2018-8
• 单位RIKEN