Journal
EUROPEAN JOURNAL OF CELL BIOLOGY
Volume 87, Issue 4, Pages 197-209Publisher
ELSEVIER GMBH
DOI: 10.1016/j.ejcb.2007.11.003
Keywords
ICA69; diabetes T1D; Rab2; ER; intermediate compartment; Golgi; trafficking; beta-COP
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Islet cell autoantigen of 69 kDa (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. (C) 2007 Elsevier GmbH. All rights reserved.
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