Apoptosis-linked gene 2 (ALG-2) is a calcium-dependent adaptor protein that is recruited to the Sec31Apositive ERES. Results: Physical association between annexin A11 and Sec31A is mediated by ALG-2, and annexin A11 is required for stable association of Sec31A at the ERES. Conclusion: Annexin A11 participates in ER-to-Golgi trafficking. Significance: Annexin A11 is the first annexin shown to modulate the early secretory pathway. Exit of cargo molecules from the endoplasmic reticulum (ER) for

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... nsport to the Golgi is the initial step in intracellular vesicular trafficking. The coat protein complex II (COPII) machinery is recruited to specialized regions of the ER, called ER exit sites (ERES), where it plays a central role in the early secretory pathway. It has been known for more than two decades that calcium is an essential factor in vesicle trafficking from the ER to Golgi apparatus. However, the role of calcium in the early secretory pathway is complicated and poorly understood. We and others previously identified Sec31A, an outer cage component of COPII, as an interacting protein for the penta-EF-hand calciumbinding protein ALG-2. In this study, we show that another calcium-binding protein, annexin A11 (AnxA11), physically associates with Sec31A by the adaptor function of ALG-2. Depletion of AnxA11 or ALG-2 decreases the population of Sec31A that is stably associated with the ERES and causes scattering of juxtanuclear ERES to the cell periphery. The synchronous ER-to-Golgi transport of transmembrane cargoes is accelerated in AnxA11-or ALG-2-knockdown cells. These findings suggest that AnxA11 maintains architectural and functional features of the ERES by coordinating with ALG-2 to stabilize Sec31A at the ERES.