Polypyrimidine tract-binding protein promotes insulin secretory granule biogenesis.
Pancreatic beta-cells store insulin in secretory granules that undergo exocytosis upon glucose stimulation. Sustained stimulation depletes beta-cells of their granule pool, which must be quickly restored. However, the factors promoting rapid granule biogenesis are unknown. Here we show that beta-cell stimulation induces the nucleocytoplasmic translocation of polypyrimidine tract-binding protein (PTB). Activated cytosolic PTB binds and stabilizes mRNAs encoding proteins of secretory granules, thus increasing their translation, whereas knockdown of PTB expression by RNA interference (RNAi) results in the depletion of secretory granules. These findings may provide insight for the understanding and treatment of diabetes, in which insulin secretion is typically impaired.
Knoch
Klaus-Peter
KP
Experimental Diabetology, Carl Gustav Carus Medical School, University of Technology Dresden, Dresden 01307, Germany.
Bergert
Hendrik
H
Borgonovo
Barbara
B
Saeger
Hans-Detlev
HD
Altkrüger
Anke
A
Verkade
Paul
P
Solimena
Michele
M
D000818:Animals; D001324:Autoantigens; D002478:Cells, Cultured; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism* / Q000648:ultrastructure; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008854:Microscopy, Electron; D038941:Polypyrimidine Tract-Binding Protein / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D021381:Protein Transport / Q000187:drug effects / Q000235:genetics; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D022142:Secretory Vesicles / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics
D001324:Autoantigens; D007328:Insulin; D008565:Membrane Proteins; D012333:RNA, Messenger; D038941:Polypyrimidine Tract-Binding Protein; D017027:Protein Tyrosine Phosphatases; C516864:Ptprn protein, rat; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D005947:Glucose