Menin localization in cell membrane compartment.

ABSTRACT

Menin is encoded by the MEN1 gene, which is mutated in an inherited human syndrome, multiple endocrine neoplasia type 1(MEN1). Menin is primarily nuclear protein, acting as a tumor suppressor in endocrine organs, but as an oncogenic factor in the mixed lineage leukemia, in a tissue-specific manner. Recently, the crystal structures of menin with different binding partners reveal menin as a key scaffold protein that functionally interacts with various partners to regulate gene transcription in the nucleus. However, outside the nucleus, menin also regulates multiple signaling pathways that traverse the cell surface membrane. The precise nature regarding to how menin associates with the membrane fraction is poorly understood. Here we show that a small fraction of menin associates with the cell membrane fraction likely via serine palmitoylation. Moreover, the majority of the membrane-associated menin may reside inside membrane vesicles, as menin is protected from trypsin-mediated proteolysis, but disruption of the membrane fraction using detergent abolishes the detection. Consistently, cellular staining for menin also reveals the distribution of menin in the cell membrane and the punctate-like cell organelles. Our findings suggest that part of intracellular menin associates with the cell membrane peripherally as well as resides within the membrane vesicles.