Extracellular Signals Induce Dynamic ER Remodeling through TAT1-dependent Microtubule Acetylation

ABSTRACT: Dynamic changes in the endoplasmic reticulum (ER) morphology are central to maintaining cellular homeostasis. Microtubules (MT) facilitate the continuous remodeling of the ER network into sheets and tubules by coordinating with many ER-shaping protein complexes, although how this process is controlled by extracellular signals remains unknown. Here we report that TAK1, a kinase responsive to various growth factors and cytokines including TGF- and TNF-, triggers ER tubulation by activating TAT1, an MT-acetylating enzyme that enhances ER-sliding. We show that this TAK1/TAT1-dependent ER remodeling promotes cell survival by actively downregulating BOK, an ER membrane-associated proapoptotic effector. While BOK is normally protected from degradation when complexed with IP3R, it is rapidly degraded upon their dissociation during the ER sheets-to-tubules conversion. These findings demonstrate a distinct mechanism of ligand-induced ER remodeling and suggest that the TAK1/TAT1 pathway may be a key target in ER stress and dysfunction.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Pancreas

SUBMITTER: Paul Langlais  

LAB HEAD: Nam Lee

PROVIDER: PXD045865 | Pride | 2024-06-16

REPOSITORIES: Pride