ICA69 is a novel Rab2 effector regulating ER-Golgi trafficking in insulinoma cells

European Journal of Cell Biology
Laura BuffaMichele Solimena

Abstract

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.

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Citations

Dec 20, 2011·Bioinformatics·Fidel RamírezMario Albrecht
Apr 17, 2012·Human Molecular Genetics·Alexander JaschkeAnnette Schürmann
Jul 10, 2013·Human Molecular Genetics·UNKNOWN Blue Mountains Eye Study (BMES), UNKNOWN Wellcome Trust Case Control Consortium 2 (WTCCC2)
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May 14, 2014·Trends in Cell Biology·Veronika ReitererHesso Farhan
Apr 4, 2019·BMC Genomics·Alberto Berral-GonzalezGuillermo Ayala

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