TMEM260 is a protein-specific O-mannosyltransferase

ABSTRACT: Mutations in the TMEM260 gene cause structural heart defects and renal anomalies syndrome (SHDRA), but the function of the encoded protein remains unknown. We report that TMEM260 is an ER-located protein O-mannosyltransferase that selectively glycosylates defined extracellular immunoglobulin, plexin, transcription factor (IPT) domains of the hepatocyte growth factor receptor (cMET), macrophage-stimulating protein receptor (RON), and plexin receptors. We demonstrate that disease-causing TMEM260 mutations impair O-mannosylation of IPT domains and that TMEM260 knock out in cells results in receptor maturation defects and abnormal growth of 3D cell models. Thus, our study identifies a new, receptor-specific O-mannosylation pathway that serves critical functions during e.g. epithelial morphogenesis.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human) Mus Musculus (mouse)

TISSUE(S): Cell Culture

SUBMITTER: Adnan Halim  

LAB HEAD: Adnan Halim

PROVIDER: PXD032328 | Pride | 2023-05-05

REPOSITORIES: Pride