Understanding the Mystery of Immune Defects

The protein Myo1f is important in regulating how quickly the immune system mobilizes to fight off infection and may help explain some infection fighting disorders, Yale School of Medicine researchers report in Science.

“To move fast immune cells should control their adhesion, or stickiness,” said Sangwon Kim, postdoctoral fellow in immunobiology and first author of the study. “It’s like installing different tires on your car for different road conditions. Immune cells quickly control their stickiness by storing integrins in the (cytoplasmic) granules and by releasing them on the surface if necessary. The more integrins on the surface, the stickier the cells.”The Yale team found in tests on mice that the Myo1f protein, which is specifically enriched in the immune system, is important in keeping this adhesion mechanism in check by preventing excess release of granules. They also found that the absence of Myo1f causes abnormally increased integrin levels on the cell surface and increased adhesion, resulting in reduced immune cell motility and impaired innate immune response against acute bacterial infection. “Without Myo1f, immune cells have too much integrin on the surface. They get too sticky and cannot move fast,” Kim said. “So the host becomes vulnerable to acute infection.”The researchers said that Myo1f seems to be involved in the formation of actin cortical networks, which support the structure near the cell surface and can work as a barrier against the release of integrins.”This work demonstrated how unconventional myosin I (Myo1f) can contribute to cell migration by integrin regulation and will help us to understand human immune defects of currently unknown origin,” said Richard Flavell, chair of immunobiology and senior author of the study.Co-authors include Wajahat Mehal, associate research scientist; Marc Pypaert, associate research scientist; Ira Mellman, professor immunobiology; Mark Mooseker, professor molecular, cellular and developmental biology, and Dianqing Wu, professor of genetics and developmental biology, University of Connecticut Health Center.(Source: Science 314: 136-139: Yale School of Medicine: October 2006.)