Myosin 1G is a hematopoietic-restricted protein highly enriched in lymphocyte plasma membrane/microvilli whose deficiency impairs lymphocyte activation (35.40)

Abstract

Abstract Class I myosins regulate diverse aspects of locomotion, vesicular traffic, and peripheral process architecture in amoeba and in mammalian cells. Mass spectrometric analysis of lymphocyte fractions enriched for plasma membrane/microvilli identified myosin 1G (Myo1G) as abundant and enriched from human peripheral blood T-cells and Myo1G plus Myo1C as abundant and enriched from a mouse pre-B-cell line. To understand its structure and function, we have investigated Myo1G by immunofluorescence, by immunoblot, by transfection of wt and mutant constructs and by creation of a knockout mouse. Myo1G is abundant in multiple hematopoietic lineages, but absent in most other cell types. Endogenous Myo1G is highly enriched at the plasma membrane and in microvilli/ruffles of lymphocytes (as is transfected Myo1G in Jurkat T-cells). Structure-function analysis with truncation and point mutants show that Myo1G localization at the membrane, like Myo1C, requires a conserved "PH-like" domain present in the tail. But unlike Myo1C, it also depends on presence of its actin-binding motor domain. Knockout mice have no obvious defect in hematopoietic cell development. However preliminary studies shown that there are defects in activation of splenic T cells after stimulation with anti TCR. Studies are in progress to elucidate the underlying mechanism by which Myo1G contributes to T-cell activation.