Characterization, chromosomal localization, and expression during hematopoietic differentiation of the gene encoding Arl6ip, ADP-ribosylation-like factor-6 interacting protein (ARL6)

Proliferation and differentiation of hematopoietic stem cells and progenitors are regulated by signals from the microenvironment, involving both secreted cytokines and adhesion molecules. The exact mechanisms by which cytokines act on hematopoietic development are still not well understood. To extend the molecular characterization of gene regulation during cytokine-induced hematopoiesis, we applied mRNA differential display to identify genes regulated when multipotent progenitor cells are allowed to differentiate into monocytes and neutrophils. Here we report the isolation and characterization of a gene that is downregulated during myeloid differentiation and encodes a 23-kDa protein with four putative transmembrane segments. The gene, which we named Arl6ip, is identical to a mouse gene recently identified by its physical interaction with ADP-ribosylation-like factor-6 (ARL6), belonging to the Ras superfamily. We add information on its full-length characterization as well as its regulation during hematopoiesis. It is expressed in all hematopoietic cell lineages, but the highest level of expression is found in early myeloid progenitor cells. Preliminary studies by immunofluorescence microscopy revealed that the ARL6IP protein is predominantly localized to intracytoplasmic membranes. This suggests an involvement of the Arl6ip gene in protein transport, membrane trafficking, or cell signaling during hematopoietic maturation.