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| Poster, Friday, 19:00 |
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| The Rho-GTPase-activating
protein myosin IXb regulates cell migration and cell-cell communication
Yan Xu1, Zhijun Liu1,
Stefanie Heinz2, Sandra Balkow2, Kay Grobe1, Mathias
Krummen2, Peter J. Hanley1, Martin Bähler1,
Stephan Grabbe2
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1
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Institute of Molecular Cell Biology,
Westfalian Wilhelms University Münster, Schloßplatz 5, 48149
Münster, Germany |
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2
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Department of Dermatology, Universitätsmedizin
Mainz, Germany |
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| Contact:
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The regulation of cell shape, cell motility and cell-cell interaction is
of major importance for immune responses. Signaling by the monomeric G-protein
Rho and the dynamic organization of the actin cytoskeleton are known to
participate in this regulation. Rho GTPases act as molecular switches,
cycling between an active GTP-bound and an inactive GDP-bound state. Myosin
IXb (Myo9b) harbors a Rho GTPase-activating protein (RhoGAP) in its tail
region that switches off Rho GTPase. Using real-time 3D chemotaxis assays,
we found that motility and gradient sensing were impaired in Myo9b-deficient
bone marrow-derived dendritic cells (DCs) in a CCL21 gradient. Consistent
with impaired motility, Myo9b-/- cutaneous DCs emigrated more
slowly than WT cells from ex vivo tissue and migrated in vivo
at a moderate rate to the draining lymph node. Moreover, we also found
that Myo9b-/- DCs exhibit a reduced capacity to stimulate T
cells both in vitro and in vivo, which might correlate with
their decreased contacts with T cells in 3D gels. These results demonstrate
that the Myo9b-mediated regulation of Rho-activity is important for the
migratory (messenger) and T cell activating functions of DCs. To address
how impaired cell migration affects immune responses, we used an animal
model of multiple sclerosis, named experimental autoimmune encephalomyelitis
(EAE) - an inflammatory, demyelinating disease of the central nervous system,
and demonstrated that Myo9b deficient mice show a delayed onset and no
recovery after MOG35-55 induced EAE. |
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