Myo1g Mediates NKR-P1C Expression in Primary Mouse NK Cells and Participates in Cytotoxicity

Myo1g, a short-tail class I myosin, has been extensively studied for its roles in cellular adhesion, migration, cytokine secretion and receptor recycling in T and B lymphocytes. However, its involvement in other immune cell populations, particularly natural killer (NK) cells, remains an open question in immunology. NKR-P1C is a type II integral membrane glycoprotein with a C-type lectin domain; it also plays roles in NK cell activation and differentiation, IFN-γ production, cytotoxic granule release. The expression of Myo1f and Myo1g mRNA in NK cells was previously found in the RIKEN database (https://gexc.riken.jp/). Thus, the present study began by confirming the presence of Myo1g protein in lysates from splenic NK cells of wild-type (WT) mice. Subsequently, it was found that mice deficient in Myo1g (Myo1g-/-) exhibited decreased frequency and absolute numbers of NK cells (defined as CD3-, CD19- and NKR-P1C+ lymphocytes) in the bone marrow, blood and spleen. Then, NK cell development was evaluated (CD122, CD49b and NKp46), demonstrating that the absence of Myo1g does not affect overall NK cell generation but does influence NKR-P1C expression. A functional analysis revealed reduced degranulation in NK cells from Myo1g-/- mice compared to WT controls. These findings were corroborated using purified NK cells, which demonstrated that NK cells from Myo1g-/- deficient mice exhibit reduced cytotoxicity. Collectively, these results suggest that Myo1g may serve as a potential target for modulating NK cell function and immune responses. To hypothesize potential mechanisms linking Myo1g to NKR-P1C expression and cytotoxicity, it is possible that Myo1g influences the stability or surface trafficking of NKR-P1C, given its known role in receptor recycling. Additionally, the absence of Myo1g could impair the cytoskeletal reorganisation required for NK cell function, affecting the formation of immunological synapses and the subsequent degranulation process.