The Hyaluronidase, TMEM2, Promotes ER Homeostasis and Longevity Independent of the UPR^ER.

ABSTRACT: Cells have evolved complex mechanisms to maintain protein homeostasis, such as the UPR^ER, which are strongly associated with several diseases and the aging process. We performed a whole-genome CRISPR-based knockout (KO) screen to identify genes important for cells to survive ER-based protein misfolding stress. We identified the cell-surface hyaluronidase (HAase), Transmembrane Protein 2 (TMEM2), as a potent modulator of ER stress resistance. The breakdown of the glycosaminoglycan, hyaluronan (HA), by TMEM2 within the extracellular matrix (ECM) altered ER stress resistance independent of canonical UPR^ER pathways but dependent upon the cell-surface receptor, CD44, a putative HA receptor, and the MAPK cell-signaling components, ERK and p38. Last, and most surprisingly, e

SUBMITTER: Schinzel RT 

PROVIDER: S-EPMC6913896 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature