O-Glycosylation regulates polarized secretion by modulating Tango1 stability

• Polarized secretion is crucial in many tissues. The conserved protein modification, O-glycosylation, plays a role in regulating secretion. However, the mechanisms by which this occurs are unknown. Here, we demonstrate that an O-glycosyltransferase functions as a novel regulator of secretion and secretory vesicle formation in vivo by glycosylating the essential Golgi/endoplasmic reticulum protein, Tango1 (Transport and Golgi organization 1), and conferring protection from furin-mediated proteolysis. Loss of the O-glycosyltransferase PGANT4 resulted in Tango1 cleavage, loss of secretory granules, and disrupted apical secretion. The secretory defects seen upon loss of pgant4 could be rescued either by overexpression of Tango1 or by knockdown of a specific furin (Dfur2) in vivo. Our studies elucidate a novel regulatory mechanism whereby secretion is influenced by the yin/yang of O-glycosylation and proteolytic cleavage. Moreover, our data have broader implications for the potential treatment of diseases resulting from the loss of O-glycosylation by modulating the activity of specific proteases.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)

Nyckelord

furin

glycosyltransferase

guanosine triphosphatase

o glycosyltransferase

protein

secretory component

tango 1 protein

unclassified drug

animal cell

article

cell membrane

cell structure

Drosophila

endoplasmic reticulum

enzyme glycosylation

essential gene

gene overexpression

Golgi complex

immunoprecipitation

mass spectrometry

nonhuman

phenotype

priority journal

protection

protein degradation

protein stability

secretion (process)

secretory cell

secretory granule

secretory vesicle

familial tumoral calcinosis

mucin

peritrophic membrane

proventriculus

Animals

Aryl Hydrocarbon Receptor Nuclear Translocator

Calcinosis

Catalysis

Drosophila melanogaster

Drosophila Proteins

Glycosylation

Golgi Apparatus

Mucins

Mutation

N-Acetylgalactosaminyltransferases

Protein Binding

Protein Processing

Post-Translational

RNA Interference

Subtilisins

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)