ICA69 is a novel Rab2 effector regulating ER-Golgi trafficking in insulinoma cells.
Islet cell autoantigen of 69kDa (ICA69) is a small GTPase-binding protein of unknown function. ICA69 is enriched in the Golgi complex and its N-terminal half contains a BAR domain, a module that can bind/bend membranes and interacts with phospholipids. Here we show that in insulinoma INS-1 cells ICA69 binds to the small GTPase Rab2, which regulates the transport of COPI vesicles between the endoplasmic reticulum and the Golgi complex. Rab2 binds to ICA69 in a GTP-dependent fashion and recruits it to membranes. Over-expression of either Rab2 or ICA69 in INS-1 cells results in a phenotype characterized by: (i) impaired anterograde transport of the secretory granule protein precursors pro-ICA512 and chromogranin A; (ii) reduction of stimulated insulin secretion. Taken together, these data identify ICA69 as a novel Rab2 effector and point to its role in regulating the early transport of insulin secretory granule proteins.
Buffa
Laura
L
Experimental Diabetology, Carl Gustav Carus School of Medicine, Dresden University of Technology, D-01307 Dresden, Germany.
Fuchs
Evelyn
E
Pietropaolo
Massimo
M
Barr
Francis
F
Solimena
Michele
M
D001324:Autoantigens / Q000378:metabolism*; D001665:Binding Sites; D045744:Cell Line, Tumor; D053379:Chromogranin A / Q000378:metabolism; D020756:Coatomer Protein / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007340:Insulinoma / Q000378:metabolism* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding; D021381:Protein Transport; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8 / Q000378:metabolism; D022142:Secretory Vesicles / Q000378:metabolism; D020693:rab2 GTP-Binding Protein / Q000378:metabolism*
D001324:Autoantigens; C506150:CHGA protein, human; D053379:Chromogranin A; D020756:Coatomer Protein; C087054:ICA1 protein, human; D007328:Insulin; C516862:PTPRN protein, human; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D020693:rab2 GTP-Binding Protein